Stem cells in tissues, organoids, and cancers.
Abstract Stem cells give rise to all cells and build the tissue structures in our body, and heterogeneity and plasticity are the hallmarks of stem cells. Epigenetic modification, which is associated with niche signals, determines stem cell differentiation and somatic cell reprogramming. Stem cells play a critical role in the development of tumors and are capable of generating 3D organoids. Understanding the properties of stem cells will improve our capacity to maintain tissue homeostasis. Dissecting epigenetic regulation could be helpful for achieving efficient cell reprograming and for developing new drugs for ca...
Source: Cellular and Molecular Life Sciences : CMLS - July 17, 2019 Category: Cytology Authors: Wang X Tags: Cell Mol Life Sci Source Type: research

Chondromodulin-1 in health, osteoarthritis, cancer, and heart disease.
Abstract The human chondromodulin-1 (Chm-1, Chm-I, CNMD, or Lect1) gene encodes a 334 amino acid type II transmembrane glycoprotein protein with characteristics of a furin cleavage site and a putative glycosylation site. Chm-1 is expressed most predominantly in healthy and developing avascular cartilage, and healthy cardiac valves. Chm-1 plays a vital role during endochondral ossification by the regulation of angiogenesis. The anti-angiogenic and chondrogenic properties of Chm-1 are attributed to its role in tissue development, homeostasis, repair and regeneration, and disease prevention. Chm-1 promotes chondrocyt...
Source: Cellular and Molecular Life Sciences : CMLS - July 17, 2019 Category: Cytology Authors: Zhu S, Qiu H, Bennett S, Kuek V, Rosen V, Xu H, Xu J Tags: Cell Mol Life Sci Source Type: research

miR-221 and -222 target CACNA1C and KCNJ5 leading to altered cardiac ion channel expression and current density.
r B Abstract MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among others cardiac hypertrophy and atrial fibrillation. The aim of our study was to evaluate the impact of miR-221/222 on cardiac electrical remodeling. Cardiac miR expression was analyzed in a mouse model with altered electrocardiography parameters and severe heart hypertrophy. Next generation sequencing revealed 14 differentially expressed miRs in hypertrophic hearts, with miR-221 and -222 being the strongest regulated miR-cluster. This increase was restricted to cardiomyocytes and not observed in cardiac fibroblasts. Ad...
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Binas S, Knyrim M, Hupfeld J, Kloeckner U, Rabe S, Mildenberger S, Quarch K, Strätz N, Misiak D, Gekle M, Grossmann C, Schreier B Tags: Cell Mol Life Sci Source Type: research

Cell-surface molecule-mediated cell-cell interactions in the regulation of ILC2-driven allergic inflammation.
Abstract Group 2 innate lymphoid cells (ILC2s) are a subset of innate immune cells that do not express antigen receptors. ILC2-mediated type 2 responses, which are mainly characterized by the production of interleukin (IL)-5 and IL-13, play key roles in inducing inflammation, protecting against infection, and maintaining tissue homeostasis. Although recent years have largely enhanced our understanding of the transcriptional networks and soluble mediators that regulate ILC2 development or function, emerging evidence suggests that ILC2s express a variety of cell-surface molecules and interact with themselves or othe...
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Lei A, Zhou J Tags: Cell Mol Life Sci Source Type: research

Src and Fyn define a new signaling cascade activated by canonical and non-canonical Wnt ligands and required for gene transcription and cell invasion.
tilde;ach M Abstract Wnt ligands signal through canonical or non-canonical signaling pathways. Although both routes share common elements, such as the Fz2 receptor, they differ in the co-receptor and in many of the final responses; for instance, whereas canonical Wnts increase β-catenin stability, non-canonical ligands downregulate it. However, both types of ligands stimulate tumor cell invasion. We show here that both the canonical Wnt3a and the non-canonical Wnt5a stimulate Fz2 tyrosine phosphorylation, Fyn binding to Fz2, Fyn activation and Fyn-dependent Stat3 phosphorylation. Wnt3a and Wnt5a require Src f...
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Villarroel A, Del Valle-Pérez B, Fuertes G, Curto J, Ontiveros N, Garcia de Herreros A, Duñach M Tags: Cell Mol Life Sci Source Type: research

Knockout of beta-2 microglobulin enhances cardiac repair by modulating exosome imprinting and inhibiting stem cell-induced immune rejection.
CONCLUSION: Our findings demonstrate that modulation of exosome's imprinting via B2M knockout is an efficient strategy to prevent the immune rejection of alloUMSCs. This study paved the way to the development of new strategies for tissue repair and regeneration without the need for HLA matching. PMID: 31312880 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Shao L, Zhang Y, Pan X, Liu B, Liang C, Zhang Y, Wang Y, Yan B, Xie W, Sun Y, Shen Z, Yu XY, Li Y Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNA PVT1 interacts with MYC and its downstream molecules to synergistically promote tumorigenesis.
Abstract Numerous studies have shown that non-coding RNAs play crucial roles in the development and progression of various tumor cells. Plasmacytoma variant translocation 1 (PVT1) mainly encodes a long non-coding RNA (lncRNA) and is located on chromosome 8q24.21, which constitutes a fragile site for genetic aberrations. PVT1 is well-known for its interaction with its neighbor MYC, which is a qualified oncogene that plays a vital role in tumorigenesis. In the past several decades, increasing attention has been paid to the interaction mechanism between PVT1 and MYC, which will benefit the clinical treatment and prog...
Source: Cellular and Molecular Life Sciences : CMLS - July 15, 2019 Category: Cytology Authors: Jin K, Wang S, Zhang Y, Xia M, Mo Y, Li X, Li G, Zeng Z, Xiong W, He Y Tags: Cell Mol Life Sci Source Type: research

The Tousled-like kinases regulate genome and epigenome stability: implications in development and disease.
Abstract The Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine-threonine kinases that have been implicated in DNA replication, DNA repair, transcription, chromatin structure, viral latency, cell cycle checkpoint control and chromosomal stability in various organisms. The functions of the TLKs appear to depend largely on their ability to regulate the H3/H4 histone chaperone ASF1, although numerous TLK substrates have been proposed. Over the last few years, a clearer picture of TLK function has emerged through the identification of new partners, the definition of specific roles in developm...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Segura-Bayona S, Stracker TH Tags: Cell Mol Life Sci Source Type: research

Impact of 17 β-HSD12, the 3-ketoacyl-CoA reductase of long-chain fatty acid synthesis, on breast cancer cell proliferation and migration.
Impact of 17β-HSD12, the 3-ketoacyl-CoA reductase of long-chain fatty acid synthesis, on breast cancer cell proliferation and migration. Cell Mol Life Sci. 2019 Jul 13;: Authors: Tsachaki M, Strauss P, Dunkel A, Navrátilová H, Mladenovic N, Odermatt A Abstract Metabolic reprogramming of tumor cells involves upregulation of fatty acid (FA) synthesis to support high bioenergetic demands and membrane synthesis. This has been shown for cytosolic synthesis of FAs with up to 16 carbon atoms. Synthesis of long-chain fatty acids (LCFAs), including ω-6 and ω-3 polyunsaturated FAs...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Tsachaki M, Strauss P, Dunkel A, Navrátilová H, Mladenovic N, Odermatt A Tags: Cell Mol Life Sci Source Type: research

Building bridges between chromosomes: novel insights into the abscission checkpoint.
Abstract In the presence of chromatin bridges, mammalian cells delay completion of cytokinesis (abscission) to prevent chromatin breakage or tetraploidization by regression of the cleavage furrow. This abscission delay is called "the abscission checkpoint" and is dependent on Aurora B kinase. Furthermore, cells stabilize the narrow cytoplasmic canal between the two daughter cells until the DNA bridges are resolved. Impaired abscission checkpoint signaling or unstable intercellular canals can lead to accumulation of DNA damage, aneuploidy, or generation of polyploid cells which are associated with tumouri...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Petsalaki E, Zachos G Tags: Cell Mol Life Sci Source Type: research

Molecular characterization of an aquaporin-2 mutation causing a severe form of nephrogenic diabetes insipidus.
This study aimed to determine the cell biological consequences of this mutation on AQP2 function. Studies were performed in HEK293 and MDCK type I cells, transfected with wildtype (WT) AQP2 or an AQP2-L137P mutant. AQP2-L137P was predominantly detected as a high-mannose form of AQP2, whereas AQP2-WT was observed in both non-glycosylated and complex glycosylated forms. In contrast to AQP2-WT, the AQP2-L137P mutant did not accumulate on the apical plasma membrane following stimulation with forskolin. Ubiquitylation of AQP2-L137P was different from AQP2-WT, with predominance of non-distinct protein bands at various molecular ...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Saglar Ozer E, Moeller HB, Karaduman T, Fenton RA, Mergen H Tags: Cell Mol Life Sci Source Type: research

Efficient base editing by RNA-guided cytidine base editors (CBEs) in pigs.
In this study, we showed that the BE4-Gam system induced the targeted C-to-T base conversion in porcine blastocysts at an efficiency of 66.7-71.4% via the injection of a single sgRNA targeting a xeno-antigen-related gene and BE4-Gam mRNA. Furthermore, the efficiency of simultaneous three gene base conversion via the injection of three targeting sgRNAs and BE4-Gam mRNA into porcine parthenogenetic embryos was 18.1%. We also obtained beta-1,4-N-acetyl-galactosaminyl transferase 2, alpha-1,3-galactosyltransferase, and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient pig by somatic cell nuclear transfe...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Yuan H, Yu T, Wang L, Yang L, Zhang Y, Liu H, Li M, Tang X, Liu Z, Li Z, Lu C, Chen X, Pang D, Ouyang H Tags: Cell Mol Life Sci Source Type: research

Biological functions and clinical applications of exosomal non-coding RNAs in hepatocellular carcinoma.
Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high mortality rate. Its dismal prognosis is attributed to late diagnosis, high risk of recurrence and drug resistance. To improve the survival of patients with HCC, new approaches are required for early diagnosis, real-time monitoring and effective treatment. Exosomes are small membranous vesicles released by most cells that contain biological molecules and play a great role in intercellular communication under physiological or pathological conditions. In cancer, exosomes from tumor cells or non-tumor cells can be tak...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2019 Category: Cytology Authors: Li C, Xu X Tags: Cell Mol Life Sci Source Type: research

Molecular control of the female germline stem cell niche size in Drosophila.
Abstract Adult stem cells have a unique capacity to renew themselves and generate differentiated cells that are needed in the body. These cells are recruited and maintained by the surrounding microenvironment, known as the stem cell niche, during organ development. Thus, the stem cell niche is required for proper tissue homeostasis, and its dysregulation is associated with tumorigenesis and tissue degeneration. The identification of niche components and the mechanisms that regulate niche establishment and maintenance, however, are just beginning to be uncovered. Germline stem cells (GSCs) of the Drosophila ovary p...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2019 Category: Cytology Authors: Hsu HJ, Bahader M, Lai CM Tags: Cell Mol Life Sci Source Type: research

Degranulation of human cytotoxic lymphocytes is a major source of proteolytically active soluble CD26/DPP4.
Abstract Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease detected on several immune cells and on epithelial cells of various organs. Besides the membrane-bound enzyme, a catalytically active soluble form (sCD26/DPP4) is detected in several body fluids. Both variants cleave off dipeptides from the N-termini of various chemokines, neuropeptides, and hormones. CD26/DPP4 plays a fundamental role in the regulation of blood glucose levels by inactivating insulinotropic incretins and CD26/DPP4 inhibitors are thus routinely used in diabetes mellitus type 2 therapy to improve glucose tolerance. Such inhibitors mig...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2019 Category: Cytology Authors: Lettau M, Dietz M, Vollmers S, Armbrust F, Peters C, Dang TM, Chitadze G, Kabelitz D, Janssen O Tags: Cell Mol Life Sci Source Type: research

Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse.
In this study, we aimed to understand the mechanisms involved in fork stability maintenance in non-transformed human cells by performing an isolation of proteins on nascent DNA-mass spectrometry analysis in hTERT-RPE cells under different replication stress conditions. Our results show that acute hydroxyurea-induced replication blockade causes the accumulation of large amounts of single-stranded DNA at the fork. Remarkably, this results in the disengagement of replisome components from nascent DNA without compromising fork restart. Notably, Cdc45-MCM-GINS helicase maintains its integrity and replisome components remain ass...
Source: Cellular and Molecular Life Sciences : CMLS - July 11, 2019 Category: Cytology Authors: Ercilla A, Feu S, Aranda S, Llopis A, Brynjólfsdóttir SH, Sørensen CS, Toledo LI, Agell N Tags: Cell Mol Life Sci Source Type: research

Correction to: Dsg2 via  Src-mediated transactivation shapes EGFR signaling towards cell adhesion.
Correction to: Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion. Cell Mol Life Sci. 2019 Jul 10;: Authors: Ungewiß H, Rötzer V, Meir M, Fey C, Diefenbacher M, Schlegel N, Waschke J Abstract In the published article, the legend for figure 3 was incorrect. The correct legend is given below. PMID: 31292664 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 10, 2019 Category: Cytology Authors: Ungewiß H, Rötzer V, Meir M, Fey C, Diefenbacher M, Schlegel N, Waschke J Tags: Cell Mol Life Sci Source Type: research

Purinergic P2Y2 receptors modulate endothelial sprouting.
Holnthoner W Abstract Purinergic P2 receptors are critical regulators of several functions within the vascular system, including platelet aggregation, vascular inflammation, and vascular tone. However, a role for ATP release and P2Y receptor signalling in angiogenesis remains poorly defined. Here, we demonstrate that blood vessel growth is controlled by P2Y2 receptors. Endothelial sprouting and vascular tube formation were significantly dependent on P2Y2 expression and inhibition of P2Y2 using a selective antagonist blocked microvascular network generation. Mechanistically, overexpression of P2Y2 in endothelial c...
Source: Cellular and Molecular Life Sciences : CMLS - July 5, 2019 Category: Cytology Authors: Mühleder S, Fuchs C, Basílio J, Szwarc D, Pill K, Labuda K, Slezak P, Siehs C, Pröll J, Priglinger E, Hoffmann C, Junger WG, Redl H, Holnthoner W Tags: Cell Mol Life Sci Source Type: research

Genomic imprinting and its effects on postnatal growth and adult metabolism.
Abstract Imprinted genes display parent-of-origin-specific expression with this epigenetic system of regulation found exclusively in therian mammals. Historically, defined imprinted gene functions were almost solely focused on pregnancy and the influence on the growth parameters of the developing embryo and placenta. More recently, a number of postnatal functions have been identified which converge on resource allocation, both for animals in the nest and in adults. While many of the prenatal functions of imprinted genes that have so far been described adhere to the "parental conflict" hypothesis, no clea...
Source: Cellular and Molecular Life Sciences : CMLS - July 3, 2019 Category: Cytology Authors: Millership SJ, Van de Pette M, Withers DJ Tags: Cell Mol Life Sci Source Type: research

Guidance of circular RNAs to proteins' behavior as binding partners.
Abstract Circular RNAs (circRNAs) are single-stranded and covalently closed back-splicing products of pre-mRNAs. They can be derived from exons, introns, or exons with intron retained between exons of transcripts, as well as antisense transcripts. CircRNAs have been reported to function as microRNA sponges, regulate gene transcription mediated by RNA polymerase II, and modulate the splicing or stability of mRNA. However, emerging studies demonstrate that they affect the behavior of proteins via direct interactions with them. Here, we summarize that by binding directly with proteins; circRNAs can facilitate their n...
Source: Cellular and Molecular Life Sciences : CMLS - July 3, 2019 Category: Cytology Authors: Luo J, Liu H, Luan S, Li Z Tags: Cell Mol Life Sci Source Type: research

Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts.
Abstract Cancers show a metabolic shift towards aerobic glycolysis. By "corrupting" their microenvironment, carcinoma cells are able to obtain energy substrates to "fuel" their mitochondrial metabolism and cell growth in an autophagy-associated, paracrine manner. However, the metabolic changes and role of normal fibroblasts in this process remain unclear. We devised a novel, indirect co-culture system to elucidate the mechanisms of metabolic coupling between stromal cells and oral squamous cell carcinoma (OSCC) cells. Here, we showed that normal oral fibroblasts (NOFs) and OSCC become metabolic...
Source: Cellular and Molecular Life Sciences : CMLS - July 3, 2019 Category: Cytology Authors: Zhang Z, Gao Z, Rajthala S, Sapkota D, Dongre H, Parajuli H, Suliman S, Das R, Li L, Bindoff LA, Costea DE, Liang X Tags: Cell Mol Life Sci Source Type: research

Cellular expression and function of naturally occurring variants of the human ABCG2 multidrug transporter.
ute;, Homolya L, Orbán TI, Sarkadi B Abstract The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics; thus the relatively frequent polymorphic and mutant ABCG2 variants in the population may significantly alter disease conditions and pharmacological effects. Low-level or non-functional ABCG2 expression may increase individual drug toxicity, reduce cancer drug resistance, and result in hyperuricemia and gout. In the present work we have studied the cellular expression, trafficking, and function of nine naturally occurring polymorphic and mutant var...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: Zámbó B, Mózner O, Bartos Z, Török G, Várady G, Telbisz Á, Homolya L, Orbán TI, Sarkadi B Tags: Cell Mol Life Sci Source Type: research

Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ  cell depletion.
Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ cell depletion. Cell Mol Life Sci. 2019 Jun 28;: Authors: La HM, Hobbs RM Abstract Mammalian spermatogenesis is a highly complex multi-step process sustained by a population of mitotic germ cells with self-renewal potential known as spermatogonial stem cells (SSCs). The maintenance and regulation of SSC function are strictly dependent on a supportive niche that is composed of multiple cell types. A detailed appreciation of the molecular mechanisms underpinning SSC activity and fate is of fundamental importance f...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: La HM, Hobbs RM Tags: Cell Mol Life Sci Source Type: research

Mechanisms of PINK1, ubiquitin and Parkin interactions in mitochondrial quality control and beyond.
Abstract Parkinson's disease (PD) is a degenerative movement disorder resulting from the loss of specific neuron types in the midbrain. Early environmental and pathophysiological studies implicated mitochondrial damage and protein aggregation as the main causes of PD. These findings are now vindicated by the characterization of more than 20 genes implicated in rare familial forms of the disease. In particular, two proteins encoded by the Parkin and PINK1 genes, whose mutations cause early-onset autosomal recessive PD, function together in a mitochondrial quality control pathway. In this review, we will describe re...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: Bayne AN, Trempe JF Tags: Cell Mol Life Sci Source Type: research

Targeted deep sequencing revealed variants in cell-free DNA of hormone receptor-positive metastatic breast cancer patients.
Abstract Cell-free DNA (cfDNA) is described to mirror intratumoral heterogeneity and gives insight about clonal evolution for improved therapeutic decisions. We sequenced cfDNA of a hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) cohort with a high coverage to examine the prevalence and relevance of any detected variant. cfDNA of 44 MBC patients was isolated, followed by library construction using a customized targeted DNA panel with integrated unique molecular indices analyzing AKT1, AR, BRCA1, BRCA2, EGFR, ERCC4, ERBB2, ERBB3, ESR1, FGFR1, KRAS, MUC16, PIK3CA, PIK3R1, PTEN, PTGFR, and TGF...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: Keup C, Benyaa K, Hauch S, Sprenger-Haussels M, Tewes M, Mach P, Bittner AK, Kimmig R, Hahn P, Kasimir-Bauer S Tags: Cell Mol Life Sci Source Type: research

Therapeutic potential of vitamin D in AGE/RAGE-related cardiovascular diseases.
This article provides a comprehensive review of the mechanistic insights into AGE/RAGE involvement in CVDs and the modulation of the AGE/RAGE signaling pathways by vitamin D. PMID: 31250032 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Lee TW, Kao YH, Chen YJ, Chao TF, Lee TI Tags: Cell Mol Life Sci Source Type: research

A novel seed plants gene regulates oxidative stress tolerance in Arabidopsis thaliana.
Abstract Oxidative stress can lead to plant growth retardation, yield loss, and death. The atr7 mutant of Arabidopsis thaliana exhibits pronounced tolerance to oxidative stress. Using positional cloning, confirmed by knockout and RNA interference (RNAi) lines, we identified the atr7 mutation and revealed that ATR7 is a previously uncharacterized gene with orthologs in other seed plants but with no homology to genes in lower plants, fungi or animals. Expression of ATR7-GFP fusion shows that ATR7 is a nuclear-localized protein. RNA-seq analysis reveals that transcript levels of genes encoding abiotic- and oxidative ...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Sujeeth N, Mehterov N, Gupta S, Qureshi MK, Fischer A, Proost S, Omidbakhshfard MA, Obata T, Benina M, Staykov N, Balazadeh S, Walther D, Fernie AR, Mueller-Roeber B, Hille J, Gechev TS Tags: Cell Mol Life Sci Source Type: research

Direct reprogramming into interneurons: potential for brain repair.
Abstract The brain tissue has only a limited capacity for generating new neurons. Therefore, to treat neurological diseases, there is a need of other cell sources for brain repair. Different sources of cells have been subject of intense research over the years, including cells from primary tissue, stem cell-derived cells and reprogrammed cells. As an alternative, direct reprogramming of resident brain cells into neurons is a recent approach that could provide an attractive method for treating brain injuries or diseases as it uses the patient's own cells for generating novel neurons inside the brain. In vivo reprog...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Pereira M, Birtele M, Rylander Ottosson D Tags: Cell Mol Life Sci Source Type: research

Bridging intestinal immunity and gut microbiota by metabolites.
Abstract The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota ...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Wang G, Huang S, Wang Y, Cai S, Yu H, Liu H, Zeng X, Zhang G, Qiao S Tags: Cell Mol Life Sci Source Type: research

The keratin-desmosome scaffold: pivotal role of desmosomes for keratin network morphogenesis.
Abstract Desmosome-anchored keratin intermediate filaments (KFs) are essential for epithelial coherence. Yet, desmosomal KF attachment and network organization are still unexplored in vivo. We, therefore, monitored KF network morphogenesis in fluorescent keratin 8 knock-in murine embryos revealing keratin enrichment at newly formed desmosomes followed by KF formation, KF elongation and KF fusion. To examine details of this process and its coupling to desmosome formation, we studied fluorescent keratin and desmosomal protein reporter dynamics in the periphery of expanding HaCaT keratinocyte colonies. Less than 3&nb...
Source: Cellular and Molecular Life Sciences : CMLS - June 26, 2019 Category: Cytology Authors: Moch M, Schwarz N, Windoffer R, Leube RE Tags: Cell Mol Life Sci Source Type: research

The assembly of succinate dehydrogenase: a key enzyme in bioenergetics.
Abstract Succinate dehydrogenase (SDH) also known as complex II or succinate:quinone oxidoreductase is an enzyme involved in both oxidative phosphorylation and tricarboxylic acid cycle; the processes that generate energy. SDH is a multi-subunit enzyme which requires a series of proteins for its proper assembly at several steps. This enzyme has medical significance as there is a broad range of human diseases from cancers to neurodegeneration related to SDH malfunction. Some of these disorders have recently been linked to defective assembly factors, reinvigorating further research in this area. Apart from that this ...
Source: Cellular and Molecular Life Sciences : CMLS - June 24, 2019 Category: Cytology Authors: Moosavi B, Berry EA, Zhu XL, Yang WC, Yang GF Tags: Cell Mol Life Sci Source Type: research

Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.
SF Abstract 'A disintegrin and metalloproteases' (ADAMs) are a family of transmembrane proteins with diverse functions in multicellular organisms. About half of the ADAMs are active metalloproteases and cleave numerous cell surface proteins, including growth factors, receptors, cytokines and cell adhesion proteins. The other ADAMs have no catalytic activity and function as adhesion proteins or receptors. Some ADAMs are ubiquitously expressed, others are expressed tissue specifically. This review highlights functions of ADAMs in the mammalian nervous system, including their links to diseases. The non-proteolytic A...
Source: Cellular and Molecular Life Sciences : CMLS - June 24, 2019 Category: Cytology Authors: Hsia HE, Tüshaus J, Brummer T, Zheng Y, Scilabra SD, Lichtenthaler SF Tags: Cell Mol Life Sci Source Type: research

Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back.
MY Abstract Human bitter taste receptors (TAS2Rs) are a subfamily of 25 G protein-coupled receptors that mediate bitter taste perception. TAS2R14 is the most broadly tuned bitter taste receptor, recognizing a range of chemically diverse agonists with micromolar-range potency. The receptor is expressed in several extra-oral tissues and is suggested to have physiological roles related to innate immune responses, male fertility, and cancer. Higher potency ligands are needed to investigate TAS2R14 function and to modulate it for future clinical applications. Here, a structure-based modeling approach is described for ...
Source: Cellular and Molecular Life Sciences : CMLS - June 24, 2019 Category: Cytology Authors: Di Pizio A, Waterloo LAW, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY Tags: Cell Mol Life Sci Source Type: research

Polyamines in mammalian pathophysiology.
da L, Urdiales JL Abstract Polyamines (PAs) are essential organic polycations for cell viability along the whole phylogenetic scale. In mammals, they are involved in the most important physiological processes: cell proliferation and viability, nutrition, fertility, as well as nervous and immune systems. Consequently, altered polyamine metabolism is involved in a series of pathologies. Due to their pathophysiological importance, PA metabolism has evolved to be a very robust metabolic module, interconnected with the other essential metabolic modules for gene expression and cell proliferation/differentiation. Two dif...
Source: Cellular and Molecular Life Sciences : CMLS - June 21, 2019 Category: Cytology Authors: Sánchez-Jiménez F, Medina MÁ, Villalobos-Rueda L, Urdiales JL Tags: Cell Mol Life Sci Source Type: research

Isorhapontigenin (ISO) inhibits stem cell-like properties and invasion of bladder cancer cell by attenuating CD44 expression.
Abstract Cancer stem cells (CSC) are highly associated with poor prognosis in cancer patients. Our previous studies report that isorhapontigenin (ISO) down-regulates SOX2-mediated cyclin D1 induction and stem-like cell properties in glioma stem-like cells. The present study revealed that ISO could inhibit stem cell-like phenotypes and invasivity of human bladder cancer (BC) by specific attenuation of expression of CD44 but not SOX-2, at both the protein transcription and degradation levels. On one hand, ISO inhibited cd44 mRNA expression through decreases in Sp1 direct binding to its promoter region-binding site, ...
Source: Cellular and Molecular Life Sciences : CMLS - June 20, 2019 Category: Cytology Authors: Luo Y, Tian Z, Hua X, Huang M, Xu J, Li J, Huang H, Cohen M, Huang C Tags: Cell Mol Life Sci Source Type: research

The molecular clock in the skin, its functionality, and how it is disrupted in cutaneous melanoma: a new pharmacological target?
Abstract The skin is the interface between the organism and the external environment, acting as its first barrier. Thus, this organ is constantly challenged by physical stimuli such as UV and infrared radiation, visible light, and temperature as well as chemicals and pathogens. To counteract the deleterious effects of the above-mentioned stimuli, the skin has complex defense mechanisms such as: immune and neuroendocrine systems; shedding of epidermal squamous layers and apoptosis of damaged cells; DNA repair; and pigmentary system. Here we have reviewed the current knowledge regarding which stimuli affect the mole...
Source: Cellular and Molecular Life Sciences : CMLS - June 20, 2019 Category: Cytology Authors: de Assis LVM, Moraes MN, de Lauro Castrucci AM Tags: Cell Mol Life Sci Source Type: research

Vps13b is required for acrosome biogenesis through functions in Golgi dynamic and membrane trafficking.
omb L Abstract The sperm acrosome is a lysosome-related organelle that develops using membrane trafficking from the Golgi apparatus as well as the endolysosomal compartment. How vesicular trafficking is regulated in spermatids to form the acrosome remains to be elucidated. VPS13B, a RAB6-interactor, was recently shown involved in endomembrane trafficking. Here, we report the generation of the first Vps13b-knockout mouse model and show that male mutant mice are infertile due to oligoasthenoteratozoospermia. This phenotype was explained by a failure of Vps13b deficient spermatids to form an acrosome. In wild-type sp...
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Da Costa R, Bordessoules M, Guilleman M, Carmignac V, Lhussiez V, Courot H, Bataille A, Chlémaire A, Bruno C, Fauque P, Thauvin C, Faivre L, Duplomb L Tags: Cell Mol Life Sci Source Type: research

Progress in the emerging role of selenoproteins in cardiovascular disease: focus on endoplasmic reticulum-resident selenoproteins.
In conclusion, selenoproteins could represent valuable targets to treat and diagnose cardiovascular diseases secondary to oxidative stress, opening a new avenue in the field of related therapeutic strategies. PMID: 31218451 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Rocca C, Pasqua T, Boukhzar L, Anouar Y, Angelone T Tags: Cell Mol Life Sci Source Type: research

The role of polarisation of circulating tumour cells in cancer metastasis.
Abstract Metastasis is the spread of cancer cells from a primary tumour to a distant site of the body. Metastasising tumour cells have to survive and readjust to different environments, such as heterogeneous solid tissues and liquid phase in lymph- or blood circulation, which they achieve through a high degree of plasticity that renders them adaptable to varying conditions. One defining characteristic of the metastatic process is the transition of tumour cells between different polarised phenotypes, ranging from differentiated epithelial polarity to migratory front-rear polarity. Here, we review the polarisation t...
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Heikenwalder M, Lorentzen A Tags: Cell Mol Life Sci Source Type: research

Protein methylation functions as the posttranslational modification switch to regulate autophagy.
Abstract Studies over the past decades have elucidated the critical role of autophagy in human health and diseases. Although the processes of autophagy in the cytoplasm have been well studied, the posttranscriptional and epigenetic regulation mechanisms of autophagy are still poorly understood. Protein methylation, including histone methylation and non-histone protein methylation, is the most important type of posttranscriptional and epigenetic modification. Recent studies have shown that protein methylation is associated with effects on autophagosome formation, autophagy-related protein expression, and signaling ...
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Li R, Wei X, Jiang DS Tags: Cell Mol Life Sci Source Type: research

MiR-17 and miR-19 cooperatively promote skeletal muscle cell differentiation.
Abstract Skeletal myogenesis is a highly coordinated process that involves cell proliferation, differentiation and fusion controlled by a complex gene regulatory network. The microRNA gene cluster miR-17-92 has been shown to be related to this process; however, the exact role of each cluster member remains unclear. Here, we show that miR-17 and miR-20a could effectively promote the differentiation of both C2C12 myoblasts and primary bovine satellite cells. In contrast, miR-18a might play a negative role in C2C12 cell differentiation, while miR-19 and miR-92a had little influence. Transcriptome and target analyses ...
Source: Cellular and Molecular Life Sciences : CMLS - June 18, 2019 Category: Cytology Authors: Kong D, He M, Yang L, Zhou R, Yan YQ, Liang Y, Teng CB Tags: Cell Mol Life Sci Source Type: research

Degradome of soluble ADAM10 and ADAM17 metalloproteases.
Abstract Disintegrin and metalloproteinases (ADAMs) 10 and 17 can release the extracellular part of a variety of membrane-bound proteins via ectodomain shedding important for many biological functions. So far, substrate identification focused exclusively on membrane-anchored ADAM10 and ADAM17. However, besides known shedding of ADAM10, we identified ADAM8 as a protease capable of releasing the ADAM17 ectodomain. Therefore, we investigated whether the soluble ectodomains of ADAM10/17 (sADAM10/17) exhibit an altered substrate spectrum compared to their membrane-bound counterparts. A mass spectrometry-based N-termino...
Source: Cellular and Molecular Life Sciences : CMLS - June 17, 2019 Category: Cytology Authors: Scharfenberg F, Helbig A, Sammel M, Benzel J, Schlomann U, Peters F, Wichert R, Bettendorff M, Schmidt-Arras D, Rose-John S, Moali C, Lichtenthaler SF, Pietrzik CU, Bartsch JW, Tholey A, Becker-Pauly C Tags: Cell Mol Life Sci Source Type: research

The molecular foundations of zygosis.
Abstract Zygosis is the generation of new biological individuals by the sexual fusion of gamete cells. Our current understanding of eukaryotic phylogeny indicates that sex is ancestral to all extant eukaryotes. Although sexual development is extremely diverse, common molecular elements have been retained. HAP2-GCS1, a protein that promotes the fusion of gamete cell membranes that is related in structure to certain viral fusogens, is conserved in many eukaryotic lineages, even though gametes vary considerably in form and behaviour between species. Similarly, although zygotes have dramatically different forms and fa...
Source: Cellular and Molecular Life Sciences : CMLS - June 15, 2019 Category: Cytology Authors: Bloomfield G Tags: Cell Mol Life Sci Source Type: research

Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding.
Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding. Cell Mol Life Sci. 2019 Jun 14;: Authors: Scharfenberg F, Armbrust F, Marengo L, Pietrzik C, Becker-Pauly C Abstract Alzheimer's Disease (AD) is the sixth-leading cause of death in industrialized countries. Neurotoxic amyloid-β (Aβ) plaques are one of the pathological hallmarks in AD patient brains. Aβ accumulates in the brain upon sequential, proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretases. However, so far disease-modifying drugs targeting β- and ...
Source: Cellular and Molecular Life Sciences : CMLS - June 14, 2019 Category: Cytology Authors: Scharfenberg F, Armbrust F, Marengo L, Pietrzik C, Becker-Pauly C Tags: Cell Mol Life Sci Source Type: research

Mechanisms of synovial joint and articular cartilage development.
Abstract Articular cartilage is formed at the end of epiphyses in the synovial joint cavity and permanently contributes to the smooth movement of synovial joints. Most skeletal elements develop from transient cartilage by a biological process known as endochondral ossification. Accumulating evidence indicates that articular and growth plate cartilage are derived from different cell sources and that different molecules and signaling pathways regulate these two kinds of cartilage. As the first sign of joint development, the interzone emerges at the presumptive joint site within a pre-cartilage tissue. After that, jo...
Source: Cellular and Molecular Life Sciences : CMLS - June 14, 2019 Category: Cytology Authors: Chijimatsu R, Saito T Tags: Cell Mol Life Sci Source Type: research

Adamts17 is involved in skeletogenesis through modulation of BMP-Smad1/5/8 pathway.
Abstract Fibrillin microfibrils are ubiquitous elements of extracellular matrix assemblies that play crucial roles in regulating the bioavailability of growth factors of the transforming growth factor beta superfamily. Recently, several "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS) proteins were shown to regulate fibrillin microfibril function. Among them, ADAMTS17 is the causative gene of Weill-Marchesani syndrome (WMS) and Weill-Marchesani-like syndrome, of which common symptoms are ectopia lentis and short stature. ADAMTS17 has also been linked to height variation in humans...
Source: Cellular and Molecular Life Sciences : CMLS - June 14, 2019 Category: Cytology Authors: Oichi T, Taniguchi Y, Soma K, Oshima Y, Yano F, Mori Y, Chijimatsu R, Kim-Kaneyama JR, Tanaka S, Saito T Tags: Cell Mol Life Sci Source Type: research

Demystifying the extracellular matrix and its proteolytic remodeling in the brain: structural and functional insights.
Abstract The extracellular matrix (ECM) plays diverse roles in several physiological and pathological conditions. In the brain, the ECM is unique both in its composition and in functions. Furthermore, almost all the cells in the central nervous system contribute to different aspects of this intricate structure. Brain ECM, enriched with proteoglycans and other small proteins, aggregate into distinct structures around neurons and oligodendrocytes. These special structures have cardinal functions in the normal functioning of the brain, such as learning, memory, and synapse regulation. In this review, we have compiled...
Source: Cellular and Molecular Life Sciences : CMLS - June 13, 2019 Category: Cytology Authors: Krishnaswamy VR, Benbenishty A, Blinder P, Sagi I Tags: Cell Mol Life Sci Source Type: research

Metalloproteinases and their tissue inhibitors in Alzheimer's disease and other neurodegenerative disorders.
Baranger K Abstract As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may soon lead to an unprecedented health, social and economic crisis. Any attempt to halt the progression of these diseases requires a thorough knowledge of the pathophysiological mechanisms involved to facilitate the identification of new targets and the application of innovative therapeutic strategies. The metzincin superfamily of metalloproteinases includes matrix metalloproteinases (MMP), a disintegrin and metalloproteinase (ADA...
Source: Cellular and Molecular Life Sciences : CMLS - June 13, 2019 Category: Cytology Authors: Rivera S, García-González L, Khrestchatisky M, Baranger K Tags: Cell Mol Life Sci Source Type: research

Open reading frame mining identifies a TLR4 binding domain in the primary sequence of ECRG4.
Abstract The embedding of small peptide ligands within large inactive pre-pro-precursor proteins encoded by orphan open reading frames (ORFs) makes them difficult to identify and study. To address this problem, we generated oligonucleotide ( 1200 amino acid EGF precursor protein or the orphan ECRG4 ORF, that encodes a 148 amino acid Esophageal Cancer Related Gene 4 (ECRG4), a putative cytokine precursor protein of up to eight ligands. After phage display and 3-4 rounds of biopanning for phage internalization into prostate cancer epithelial cells, sequencing identified the 53-amino acid EGF ligand encoded by...
Source: Cellular and Molecular Life Sciences : CMLS - June 12, 2019 Category: Cytology Authors: Dang X, Coimbra R, Mao L, Podvin S, Li X, Yu H, Costantini TW, Zeng X, Larocca D, Eliceiri BP, Baird A Tags: Cell Mol Life Sci Source Type: research

Metalloproteinases mediate diabetes-induced retinal neuropathy and vasculopathy.
Abstract Matrix metalloproteinases (MMPs) and related metalloproteinases with a disintegrin domain (ADAMs) have become interesting probes and targets in eye diseases, including diabetic retinopathy. We here summarize recent data about MMPs and ADAMs in retinopathies. Retinal diseases range from rare genetic afflictions to diabetic retinopathy, the latter of which is reaching epidemic proportions. MMPs and ADAMs play roles in normal eye development and in disease states, not only in local proteolysis but also signaling functions mediated by specific protein domains, interacting with cell surface receptors. In proli...
Source: Cellular and Molecular Life Sciences : CMLS - June 10, 2019 Category: Cytology Authors: Opdenakker G, Abu El-Asrar A Tags: Cell Mol Life Sci Source Type: research