Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.
Abstract Polyglutamine (polyQ) diseases are incurable neurological disorders caused by CAG repeat expansion in the open reading frames (ORFs) of specific genes. This type of mutation in the HTT gene is responsible for Huntington's disease (HD). CAG repeat-targeting artificial miRNAs (art-miRNAs) were shown as attractive therapeutic approach for polyQ disorders as they caused allele-selective decrease in the level of mutant proteins. Here, using polyQ disease models, we aimed to demonstrate how miRNA-based gene expression regulation is dependent on target sequence features. We show that the silencing efficiency and...
Source: Cellular and Molecular Life Sciences : CMLS - July 21, 2020 Category: Cytology Authors: Ciesiolka A, Stroynowska-Czerwinska A, Joachimiak P, Ciolak A, Kozlowska E, Michalak M, Dabrowska M, Olejniczak M, Raczynska KD, Zielinska D, Wozna-Wysocka M, Krzyzosiak WJ, Fiszer A Tags: Cell Mol Life Sci Source Type: research

Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance.
Abstract Histone deacetylases (HDACs) are conserved enzymes that regulate many cellular processes by catalyzing the removal of acetyl groups from lysine residues on histones and non-histone proteins. As appropriate for proteins that occupy such an essential biological role, HDAC activities and functions are in turn highly regulated. Overwhelming evidence suggests that the dysregulation of HDACs plays a major role in many human diseases. The regulation of HDACs is achieved by multiple different mechanisms, including posttranslational modifications. One of the most common posttranslational modifications on HDACs is ...
Source: Cellular and Molecular Life Sciences : CMLS - July 18, 2020 Category: Cytology Authors: Bahl S, Seto E Tags: Cell Mol Life Sci Source Type: research

NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor.
NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor. Cell Mol Life Sci. 2020 Jul 16;: Authors: Mazzaferro S, Whiteman ST, Alcaino C, Beyder A, Sine SM Abstract Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of pentameric ligand-gated ion channels, and in neuronal tissues, are assembled from various types of α- and β-subunits. Furthermore, the subunits α4 and β2 assemble in two predominant stoichiometric forms, (α4)2(β2)3 and (α4)3(β2)2, forming receptors with dramatically...
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2020 Category: Cytology Authors: Mazzaferro S, Whiteman ST, Alcaino C, Beyder A, Sine SM Tags: Cell Mol Life Sci Source Type: research

Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation.
Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation. Cell Mol Life Sci. 2020 Jul 15;: Authors: Nam MH, Won W, Han KS, Lee CJ Abstract μ-opioid receptor (MOR) is a class of opioid receptors that is critical for analgesia, reward, and euphoria. MOR is distributed in various brain regions, including the hippocampus, where traditionally, it is believed to be localized mainly at the presynaptic terminals of the GABAergic inhibitory interneurons to exert a strong disinhibitory effect on excitatory pyramidal neurons. However, recent i...
Source: Cellular and Molecular Life Sciences : CMLS - July 15, 2020 Category: Cytology Authors: Nam MH, Won W, Han KS, Lee CJ Tags: Cell Mol Life Sci Source Type: research

Structure-function analysis of naturally occurring apolipoprotein A-I L144R, A164S and L178P mutants provides insight on their role on HDL levels and cardiovascular risk.
Abstract Naturally occurring point mutations in apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), may affect plasma HDL-cholesterol levels and cardiovascular risk. Here, we evaluated the effect of human apoA-I mutations L144R (associated with low HDL-cholesterol), L178P (associated with low HDL-cholesterol and increased cardiovascular risk) and A164S (associated with increased cardiovascular risk and mortality without low HDL-cholesterol) on the structural integrity and functions of lipid-free and lipoprotein-associated apoA-I in an effort to explain the phenotypes of subj...
Source: Cellular and Molecular Life Sciences : CMLS - July 14, 2020 Category: Cytology Authors: Gkolfinopoulou C, Soukou F, Dafnis I, Kellici TF, Sanoudou D, Mavromoustakos T, Stratikos E, Chroni A Tags: Cell Mol Life Sci Source Type: research

Correction to: The effect of fornix deep brain stimulation in brain diseases.
Abstract After publication of the original article it came to the authors' attention that there was an error under the subheading Traumatic Brain Injury (TBI) as well as Table 1. PMID: 32661560 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 14, 2020 Category: Cytology Authors: Liu H, Temel Y, Boonstra J, Hescham S Tags: Cell Mol Life Sci Source Type: research

The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens.
Abstract Neutrophils are predominant immune cells that protect the human body against infections by deploying sophisticated antimicrobial strategies including phagocytosis of bacteria and neutrophil extracellular trap (NET) formation. Here, we provide an overview of the mechanisms by which neutrophils kill exogenous pathogens before we focus on one particular weapon in their arsenal: the generation of the oxidizing hypohalous acids HOCl, HOBr and HOSCN during the so-called oxidative burst by the enzyme myeloperoxidase. We look at the effects of these hypohalous acids on biological systems in general and proteins i...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2020 Category: Cytology Authors: Ulfig A, Leichert LI Tags: Cell Mol Life Sci Source Type: research

Metabolic crosstalk in the tumor microenvironment regulates antitumor immunosuppression and immunotherapy resisitance.
Abstract The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. In addition, tumor-derived metabolites regulate the activa...
Source: Cellular and Molecular Life Sciences : CMLS - July 11, 2020 Category: Cytology Authors: Wei F, Wang D, Wei J, Tang N, Tang L, Xiong F, Guo C, Zhou M, Li X, Li G, Xiong W, Zhang S, Zeng Z Tags: Cell Mol Life Sci Source Type: research

Bassoon inhibits proteasome activity via interaction with PSMB4.
ova A Abstract Proteasomes are protein complexes that mediate controlled degradation of damaged or unneeded cellular proteins. In neurons, proteasome regulates synaptic function and its dysfunction has been linked to neurodegeneration and neuronal cell death. However, endogenous mechanisms controlling proteasomal activity are insufficiently understood. Here, we describe a novel interaction between presynaptic scaffolding protein bassoon and PSMB4, a β subunit of the 20S core proteasome. Expression of bassoon fragments that interact with PSMB4 in cell lines or in primary neurons attenuates all endopeptidase ac...
Source: Cellular and Molecular Life Sciences : CMLS - July 10, 2020 Category: Cytology Authors: Montenegro-Venegas C, Fienko S, Anni D, Pina-Fernández E, Frischknecht R, Fejtova A Tags: Cell Mol Life Sci Source Type: research

Macroglial diversity: white and grey areas and relevance to remyelination.
Abstract Macroglia, comprising astrocytes and oligodendroglial lineage cells, have long been regarded as uniform cell types of the central nervous system (CNS). Although regional morphological differences between these cell types were initially described after their identification a century ago, these differences were largely ignored. Recently, accumulating evidence suggests that macroglial cells form distinct populations throughout the CNS, based on both functional and morphological features. Moreover, with the use of refined techniques including single-cell and single-nucleus RNA sequencing, additional evidence ...
Source: Cellular and Molecular Life Sciences : CMLS - July 9, 2020 Category: Cytology Authors: Werkman IL, Lentferink DH, Baron W Tags: Cell Mol Life Sci Source Type: research

RBM38 in cancer: role and mechanism.
Abstract Cancer is the second leading cause of death globally. Abnormity in gene expression regulation characterizes the trajectory of tumor development and progression. RNA-binding proteins (RBPs) are widely dysregulated, and thus implicated, in numerous human cancers. RBPs mainly regulate gene expression post-transcriptionally, but emerging studies suggest that many RBPs can impact transcription by acting on chromatin as transcription factors (TFs) or cofactors. Here, we review the evidence that RBM38, an intensively studied RBP, frequently plays a tumor-suppressive role in multiple human cancer types. Genetic s...
Source: Cellular and Molecular Life Sciences : CMLS - July 8, 2020 Category: Cytology Authors: Zou C, Wan Y, He L, Zheng JH, Mei Y, Shi J, Zhang M, Dong Z, Zhang D Tags: Cell Mol Life Sci Source Type: research

Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family.
Abstract AlkB homologs (ALKBH) are a family of specific demethylases that depend on Fe2+ and α-ketoglutarate to catalyze demethylation on different substrates, including ssDNA, dsDNA, mRNA, tRNA, and proteins. Previous studies have made great progress in determining the sequence, structure, and molecular mechanism of the ALKBH family. Here, we first review the multi-substrate selectivity of the ALKBH demethylase family from the perspective of sequence and structural evolution. The construction of the phylogenetic tree and the comparison of key loops and non-homologous domains indicate that the paralogs with ...
Source: Cellular and Molecular Life Sciences : CMLS - July 8, 2020 Category: Cytology Authors: Xu B, Liu D, Wang Z, Tian R, Zuo Y Tags: Cell Mol Life Sci Source Type: research

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies.
Abstract The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights...
Source: Cellular and Molecular Life Sciences : CMLS - July 4, 2020 Category: Cytology Authors: Mercurio I, Tragni V, Busto F, De Grassi A, Pierri CL Tags: Cell Mol Life Sci Source Type: research

Glial cells in Parkinson ´s disease: protective or deleterious?
Glial cells in Parkinson´s disease: protective or deleterious? Cell Mol Life Sci. 2020 Jul 02;: Authors: Domingues AV, Pereira IM, Vilaça-Faria H, Salgado AJ, Rodrigues AJ, Teixeira FG Abstract Glial cells have been identified more than 100 years ago, and are known to play a key role in the central nervous system (CNS) function. A recent piece of evidence is emerging showing that in addition to the capacity of CNS modulation and homeostasis, glial cells are also being looked like as a promising cell source not only to study CNS pathologies initiation and progression but also to the e...
Source: Cellular and Molecular Life Sciences : CMLS - July 2, 2020 Category: Cytology Authors: Domingues AV, Pereira IM, Vilaça-Faria H, Salgado AJ, Rodrigues AJ, Teixeira FG Tags: Cell Mol Life Sci Source Type: research

Neural glycomics: the sweet side of nervous system functions.
We describe the isolation of such mimetic compounds using not only Western NIH, but also traditional Chinese medical libraries. With this review, we hope to deepen the interests in this exciting field. PMID: 32613283 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 1, 2020 Category: Cytology Authors: Sytnyk V, Leshchyns'ka I, Schachner M Tags: Cell Mol Life Sci Source Type: research

The proteostasis guardian HSF1 directs the transcription of its paralog and interactor HSF2 during proteasome dysfunction.
Abstract Protein homeostasis is essential for life in eukaryotes. Organisms respond to proteotoxic stress by activating heat shock transcription factors (HSFs), which play important roles in cytoprotection, longevity and development. Of six human HSFs, HSF1 acts as a proteostasis guardian regulating stress-induced transcriptional responses, whereas HSF2 has a critical role in development, in particular of brain and reproductive organs. Unlike HSF1, that is a stable protein constitutively expressed, HSF2 is a labile protein and its expression varies in different tissues; however, the mechanisms regulating HSF2 expr...
Source: Cellular and Molecular Life Sciences : CMLS - June 30, 2020 Category: Cytology Authors: Santopolo S, Riccio A, Rossi A, Santoro MG Tags: Cell Mol Life Sci Source Type: research

Plexin-Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme.
k M Abstract Plexins receive guidance cues from semaphorin ligands and transmit their signal through the plasma membrane. This family of proteins is unique amongst single-pass transmembrane receptors as their intracellular regions interact directly with several small GTPases, which regulate cytoskeletal dynamics and cell adhesion. Here, we characterize the GTPase Activating Protein (GAP) function of Plexin-B1 and find that a cooperative GAP activity towards the substrate GTPase, Rap1b, is associated with the N-terminal Juxtamembrane region of Plexin-B1. Importantly, we unveil an activation mechanism of Plexin-B1 b...
Source: Cellular and Molecular Life Sciences : CMLS - June 29, 2020 Category: Cytology Authors: Li ZL, Müller-Greven J, Kim S, Tamagnone L, Buck M Tags: Cell Mol Life Sci Source Type: research

Engineered-extracellular vesicles as an optimistic tool for microRNA delivery for osteoarthritis treatment.
Abstract Worldwide, osteoarthritis (OA) is one of the most common chronic diseases. In OA, profiling gene expression changes occur and cartilage tissue homeostasis is lost. Suggestions for OA treatment include regulation of gene expressions via the use of microRNAs (miRNAs). However, problems exist with the use of miRNAs, the most important of which is the delivery of sufficient amounts of effective miRNAs to save cartilage tissue. The engineering of extracellular vesicles (EVs) with the use of advanced techniques would be an efficient OA treatment. Therefore, we discuss the importance of miRNAs in terms of cartil...
Source: Cellular and Molecular Life Sciences : CMLS - June 29, 2020 Category: Cytology Authors: Esmaeili A, Hosseini S, Baghaban Eslaminejad M Tags: Cell Mol Life Sci Source Type: research

Targeting the pathways of regulated necrosis: a potential strategy for alleviation of cardio-cerebrovascular injury.
Abstract Apoptosis, necrosis and autophagy-dependent cell death are the three major types of cell death. Traditionally, necrosis is thought as a passive and unregulated form of cell death. However, certain necrosis can also occur in a highly regulated manner, referring to regulated necrosis. Depending on the signaling pathways, regulated necrosis can be further classified as necroptosis, pyroptosis, ferroptosis, parthanatos and CypD-mediated necrosis. Numerous studies have reported that regulated necrosis contributes to the progression of multiple injury-relevant diseases. For example, necroptosis contributes to t...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2020 Category: Cytology Authors: Lu LQ, Tian J, Luo XJ, Peng J Tags: Cell Mol Life Sci Source Type: research

Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.
do MF Abstract Diabetes affects millions of people worldwide. This devastating disease dramatically increases the risk of developing cardiovascular disorders. A hallmark metabolic abnormality in diabetes is hyperglycemia, which contributes to the pathogenesis of cardiovascular complications. These cardiovascular complications are, at least in part, related to hyperglycemia-induced molecular and cellular changes in the cells making up blood vessels. Whereas the mechanisms mediating endothelial dysfunction during hyperglycemia have been extensively examined, much less is known about how hyperglycemia impacts vascula...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2020 Category: Cytology Authors: Nieves-Cintrón M, Flores-Tamez VA, Le T, Baudel MM, Navedo MF Tags: Cell Mol Life Sci Source Type: research

L-serine synthesis via the phosphorylated pathway in humans.
Abstract L-serine is a nonessential amino acid in eukaryotic cells, used for protein synthesis and in producing phosphoglycerides, glycerides, sphingolipids, phosphatidylserine, and methylenetetrahydrofolate. Moreover, L-serine is the precursor of two relevant coagonists of NMDA receptors: glycine (through the enzyme serine hydroxymethyltransferase), which preferentially acts on extrasynaptic receptors and D-serine (through the enzyme serine racemase), dominant at synaptic receptors. The cytosolic "phosphorylated pathway" regulates de novo biosynthesis of L-serine, employing 3-phosphoglycerate generated ...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2020 Category: Cytology Authors: Murtas G, Marcone GL, Sacchi S, Pollegioni L Tags: Cell Mol Life Sci Source Type: research

KHK inhibition for the treatment of hereditary fructose intolerance and nonalcoholic fatty liver disease: a double-edged sword.
PMID: 32591859 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 26, 2020 Category: Cytology Authors: Pinheiro FC, Sperb-Ludwig F, Schwartz IVD Tags: Cell Mol Life Sci Source Type: research

ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.
lou C Abstract The innate immune response constitutes the first line of defense against pathogens. It involves the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), the production of inflammatory cytokines and the recruitment of immune cells to infection sites. Recently, ADP-heptose, a soluble intermediate of the lipopolysaccharide biosynthetic pathway in Gram-negative bacteria, has been identified by several research groups as a PAMP. Here, we recapitulate the evidence that led to this identification and discuss the controversy over the immunogenic properties ...
Source: Cellular and Molecular Life Sciences : CMLS - June 26, 2020 Category: Cytology Authors: García-Weber D, Arrieumerlou C Tags: Cell Mol Life Sci Source Type: research

Functional impact of HIV-1 Tat on cells of the CNS and its role in HAND.
Abstract Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) is a potent mediator involved in the development of HIV-1-associated neurocognitive disorders (HAND). Tat is expressed even in the presence of antiretroviral therapy (ART) and is able to enter the central nervous system (CNS) through a variety of ways, where Tat can interact with microglia, astrocytes, brain microvascular endothelial cells, and neurons. The presence of low concentrations of extracellular Tat alone has been shown to lead to dysregulated gene expression, chronic cell activation, inflammation, neurotoxicity, an...
Source: Cellular and Molecular Life Sciences : CMLS - June 23, 2020 Category: Cytology Authors: Marino J, Maubert ME, Mele AR, Spector C, Wigdahl B, Nonnemacher MR Tags: Cell Mol Life Sci Source Type: research

New insights into anti-M üllerian hormone role in the hypothalamic-pituitary-gonadal axis and neuroendocrine development.
New insights into anti-Müllerian hormone role in the hypothalamic-pituitary-gonadal axis and neuroendocrine development. Cell Mol Life Sci. 2020 Jun 20;: Authors: Silva MSB, Giacobini P Abstract Research into the physiological actions of anti-Müllerian hormone (AMH) has rapidly expanded from its classical role in male sexual differentiation to the regulation of ovarian function, routine clinical use in reproductive health and potential use as a biomarker in the diagnosis of polycystic ovary syndrome (PCOS). During the past 10 years, the notion that AMH could act exclusively at gonadal l...
Source: Cellular and Molecular Life Sciences : CMLS - June 20, 2020 Category: Cytology Authors: Silva MSB, Giacobini P Tags: Cell Mol Life Sci Source Type: research

KDEL receptor is a cell surface receptor that cycles between the plasma membrane and the Golgi via clathrin-mediated transport carriers.
In this study, we used N-terminally Halo-tagged KDEL receptor to investigate its endocytosis from the plasma membrane and trafficking itinerary of the endocytosed receptor through the endolysosomal compartments. Our results indicate that surface-expressed KDEL receptor undergoes highly complex recycling pathways via the Golgi and peri-nuclear recycling endosomes that are positive for Rab11 and Rab14, respectively. Unexpectedly, KDEL receptor appears to preferentially utilize clathrin-mediated endocytic pathway as well as clathrin-dependent transport carriers for export from the trans-Golgi network. Taken together, we sugge...
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2020 Category: Cytology Authors: Jia J, Yue X, Zhu L, Jing S, Wang Y, Gim B, Qian Y, Lee I Tags: Cell Mol Life Sci Source Type: research

Epigenetic control of natriuretic peptides: implications for health and disease.
Abstract The natriuretic peptides (NPs) family, including a class of hormones and their receptors, is largely known for its beneficial effects within the cardiovascular system to preserve regular functions and health. The concentration level of each component of the family is of crucial importance to guarantee a proper control of both systemic and local cardiovascular functions. A fine equilibrium between gene expression, protein secretion and clearance is needed to achieve the final optimal level of NPs. To this aim, the regulation of gene expression and translation plays a key role. In this regard, we know the e...
Source: Cellular and Molecular Life Sciences : CMLS - June 18, 2020 Category: Cytology Authors: Rubattu S, Stanzione R, Cotugno M, Bianchi F, Marchitti S, Forte M Tags: Cell Mol Life Sci Source Type: research

Revisiting respiratory syncytial virus's interaction with host immunity, towards novel therapeutics.
Abstract Every year there are > 33 million cases of Respiratory Syncytial Virus (RSV)-related respiratory infection in children under the age of five, making RSV the leading cause of lower respiratory tract infection (LRTI) in infants. RSV is a global infection, but 99% of related mortality is in low/middle-income countries. Unbelievably, 62 years after its identification, there remains no effective treatment nor vaccine for this deadly virus, leaving infants, elderly and immunocompromised patients at high risk. The success of all pathogens depends on their ability to evade and modulate the h...
Source: Cellular and Molecular Life Sciences : CMLS - June 16, 2020 Category: Cytology Authors: Efstathiou C, Abidi SH, Harker J, Stevenson NJ Tags: Cell Mol Life Sci Source Type: research

Tumour dormancy in inflammatory microenvironment: A promising therapeutic strategy for cancer-related bone metastasis.
Abstract Cancer metastasis is a unique feature of malignant tumours. Even bone can become a common colonization site due to the tendency of solid tumours, including breast cancer (BCa) and prostate cancer (PCa), to metastasize to bone. Currently, a previous concept in tumour metabolism called tumour dormancy may be a promising target for antitumour treatment. When disseminated tumour cells (DTCs) metastasize to the bone microenvironment, they form a flexible regulatory network called the "bone-tumour-inflammation network". In this network, bone turnover as well as metabolism, tumour progression, angiogen...
Source: Cellular and Molecular Life Sciences : CMLS - June 16, 2020 Category: Cytology Authors: Hu W, Zhang L, Dong Y, Tian Z, Chen Y, Dong S Tags: Cell Mol Life Sci Source Type: research

How much, if anything, do we know about sperm chromosomes of Robertsonian translocation carriers?
Abstract In men with oligozoospermia, Robertsonian translocations (RobTs) are the most common type of autosomal aberrations. The most commonly occurring types are rob(13;14) and rob(14;21), and other types of RobTs are described as 'rare' cases. Based on molecular research, all RobTs can be broadly classified into Class 1 and Class 2. Class 1 translocations produce the same breakpoints within their RobT type, but Class 2 translocations are predicted to form during meiosis or mitosis through a variety of mechanisms, resulting in variation in the breakpoint locations. This review seeks to analyse the available data ...
Source: Cellular and Molecular Life Sciences : CMLS - June 8, 2020 Category: Cytology Authors: Wiland E, Olszewska M, Woźniak T, Kurpisz M Tags: Cell Mol Life Sci Source Type: research

How CD40L reverse signaling regulates axon and dendrite growth.
Abstract CD40-activated CD40L reverse signaling is a major physiological regulator of axon and dendrite growth from developing hippocampal pyramidal neurons. Here we have studied how CD40L-mediated reverse signaling promotes the growth of these processes. Cultures of hippocampal pyramidal neurons were established from Cd40-/- mouse embryos to eliminate endogenous CD40/CD40L signaling, and CD40L reverse signaling was stimulated by a CD40-Fc chimera. CD40L reverse signaling increased phosphorylation and hence activation of proteins in the PKC, ERK, and JNK signaling pathways. Pharmacological activators and inhibitor...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2020 Category: Cytology Authors: Carriba P, Davies AM Tags: Cell Mol Life Sci Source Type: research

Metabolic heterogeneity and adaptability in brain tumors.
Abstract The metabolic complexity and flexibility commonly observed in brain tumors, especially glioblastoma, is fundamental for their development and progression. The ability of tumor cells to modify their genetic landscape and adapt metabolically, subverts therapeutic efficacy, and inevitably instigates therapeutic resistance. To overcome these challenges and develop effective therapeutic strategies targeting essential metabolic processes, it is necessary to identify the mechanisms underlying heterogeneity and define metabolic preferences and liabilities of malignant cells. In this review, we will discuss metabo...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2020 Category: Cytology Authors: Badr CE, Silver DJ, Siebzehnrubl FA, Deleyrolle LP Tags: Cell Mol Life Sci Source Type: research

A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine : "A gut feeling".
A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine : "A gut feeling". Cell Mol Life Sci. 2020 Jun 06;: Authors: Elferink H, Bruekers JPJ, Veeneman GH, Boltje TJ Abstract The human body is able to process and transport a complex variety of carbohydrates, unlocking their nutritional value as energy source or as important building block. The endogenous glycosyl hydrolases (glycosidases) and glycosyl transporter proteins located in the enterocytes of the small intestine play a crucial role in this process and digest and/or transport ...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2020 Category: Cytology Authors: Elferink H, Bruekers JPJ, Veeneman GH, Boltje TJ Tags: Cell Mol Life Sci Source Type: research

Contribution of neural crest-derived stem cells and nasal chondrocytes to articular cartilage regeneration.
Abstract Due to poor self-regenerative potential of articular cartilage, stem cell-based regeneration becomes a hopeful approach for the treatment of articular cartilage defects. Recent studies indicate that neural crest-derived cells (NCDCs) have the potential for repairing articular cartilage with even greater chondrogenic capacity than mesoderm-derived cells (MDCs): a conventional stem cell source for cartilage regeneration. Given that NCDCs originate from a different germ layer in the early embryo compared with MDCs that give rise to articular cartilage, a mystery remains regarding their capacity for articular...
Source: Cellular and Molecular Life Sciences : CMLS - June 5, 2020 Category: Cytology Authors: Li T, Chen S, Pei M Tags: Cell Mol Life Sci Source Type: research

Stress granule subtypes: an emerging link to neurodegeneration.
Abstract Stress Granules (SGs) are membraneless cytoplasmic RNA granules, which contain translationally stalled mRNAs, associated translation initiation factors and multiple RNA-binding proteins (RBPs). They are formed in response to various stresses and contribute to reprogramming of cellular metabolism to aid cell survival. Because of their cytoprotective nature, association with translation regulation and cell signaling, SGs are an essential component of the integrated stress response pathway, a complex adaptive program central to stress management. Recent advances in SG biology unambiguously demonstrate t...
Source: Cellular and Molecular Life Sciences : CMLS - June 4, 2020 Category: Cytology Authors: Advani VM, Ivanov P Tags: Cell Mol Life Sci Source Type: research

Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress.
Abstract The results of different human epidemiological datasets provided the impetus to introduce the now commonly accepted theory coined as 'developmental programming', whereby the presence of a stressor during gestation predisposes the growing fetus to develop diseases, such as metabolic dysfunction in later postnatal life. However, in a clinical setting, human lifespan and inaccessibility to tissue for analysis are major limitations to study the molecular mechanisms governing developmental programming. Subsequently, studies using animal models have proved indispensable to the identification of key molecular pa...
Source: Cellular and Molecular Life Sciences : CMLS - June 3, 2020 Category: Cytology Authors: Christoforou ER, Sferruzzi-Perri AN Tags: Cell Mol Life Sci Source Type: research

Saccharomyces cerevisiae rDNA as super-hub: the region where replication, transcription and recombination meet.
Abstract Saccharomyces cerevisiae ribosomal DNA, the repeated region where rRNAs are synthesized by about 150 encoding units, hosts all the protein machineries responsible for the main DNA transactions such as replication, transcription and recombination. This and its repetitive nature make rDNA a unique and complex genetic locus compared to any other. All the different molecular machineries acting in this locus need to be accurately and finely controlled and coordinated and for this reason rDNA is one of the most impressive examples of highly complex molecular regulated loci. The region in which the large molecul...
Source: Cellular and Molecular Life Sciences : CMLS - May 31, 2020 Category: Cytology Authors: Egidi A, Di Felice F, Camilloni G Tags: Cell Mol Life Sci Source Type: research

Core cell cycle machinery is crucially involved in both life and death of post-mitotic neurons.
Abstract A persistent dogma in neuroscience supported the idea that terminally differentiated neurons permanently withdraw from the cell cycle. However, since the late 1990s, several studies have shown that cell cycle proteins are expressed in post-mitotic neurons under physiological conditions, indicating that the cell cycle machinery is not restricted to proliferating cells. Moreover, many studies have highlighted a clear link between cell cycle-related proteins and neurological disorders, particularly relating to apoptosis-induced neuronal death. Indeed, cell cycle-related proteins can be upregulated or overact...
Source: Cellular and Molecular Life Sciences : CMLS - May 31, 2020 Category: Cytology Authors: Marlier Q, D'aes T, Verteneuil S, Vandenbosch R, Malgrange B Tags: Cell Mol Life Sci Source Type: research

Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors.
Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors. Cell Mol Life Sci. 2020 May 29;: Authors: Prevost MS, Bouchenaki H, Barilone N, Gielen M, Corringer PJ Abstract Nicotinic acetylcholine receptors (nAChRs) are pentameric ion channels expressed in the central nervous systems. nAChRs containing the α4, β2 and α5 subunits are specifically involved in addictive processes, but their functional architecture is poorly understood due to the intricacy of assembly of these subunits. Here we constrained the subunit assembly by designing fully concatenated ...
Source: Cellular and Molecular Life Sciences : CMLS - May 29, 2020 Category: Cytology Authors: Prevost MS, Bouchenaki H, Barilone N, Gielen M, Corringer PJ Tags: Cell Mol Life Sci Source Type: research

The role of SIRT3-mediated mitochondrial homeostasis in osteoarthritis.
Abstract Osteoarthritis is the most common degenerative joint disease and causes major pain and disability in adults. It has been reported that mitochondrial dysfunction in chondrocytes is associated with osteoarthritis. Sirtuins are a family of nicotinamide adenine dinucleotide-dependent histone deacetylases that have the ability to deacetylate protein targets and play an important role in the regulation of cell physiological and pathological processes. Among sirtuin family members, sirtuin 3, which is mainly located in mitochondria, can exert its deacetylation activity to regulate mitochondrial function, regener...
Source: Cellular and Molecular Life Sciences : CMLS - May 28, 2020 Category: Cytology Authors: He Y, Wu Z, Xu L, Xu K, Chen Z, Ran J, Wu L Tags: Cell Mol Life Sci Source Type: research

Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2.
Abstract Recent studies suggest that synaptic lysophosphatidic acids (LPAs) augment glutamate-dependent cortical excitability and sensory information processing in mice and humans via presynaptic LPAR2 activation. Here, we studied the consequences of LPAR2 deletion or antagonism on various aspects of cognition using a set of behavioral and electrophysiological analyses. Hippocampal neuronal network activity was decreased in middle-aged LPAR2-/- mice, whereas hippocampal long-term potentiation (LTP) was increased suggesting cognitive advantages of LPAR2-/- mice. In line with the lower excitability, RNAseq studies r...
Source: Cellular and Molecular Life Sciences : CMLS - May 28, 2020 Category: Cytology Authors: Fischer C, Endle H, Schumann L, Wilken-Schmitz A, Kaiser J, Gerber S, Vogelaar CF, Schmidt MHH, Nitsch R, Snodgrass I, Thomas D, Vogt J, Tegeder I Tags: Cell Mol Life Sci Source Type: research

Updating dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2): molecular basis, functions and role in diseases.
ntilde;oz E, Calzado MA Abstract Members of the dual-specificity tyrosine-regulated kinase (DYRKs) subfamily possess a distinctive capacity to phosphorylate tyrosine, serine, and threonine residues. Among the DYRK class II members, DYRK2 is considered a unique protein due to its role in disease. According to the post-transcriptional and post-translational modifications, DYRK2 expression greatly differs among human tissues. Regarding its mechanism of action, this kinase performs direct phosphorylation on its substrates or acts as a priming kinase, enabling subsequent substrate phosphorylation by GSK3β. Moreove...
Source: Cellular and Molecular Life Sciences : CMLS - May 27, 2020 Category: Cytology Authors: Correa-Sáez A, Jiménez-Izquierdo R, Garrido-Rodríguez M, Morrugares R, Muñoz E, Calzado MA Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNAs in cutaneous biology  and keratinocyte carcinomas.
Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas. Cell Mol Life Sci. 2020 May 27;: Authors: Piipponen M, Nissinen L, Kähäri VM Abstract Long non-coding RNAs (lncRNAs) are a largely uncharacterized group of non-coding RNAs with diverse regulatory roles in various biological processes. Recent observations have elucidated the functional roles of lncRNAs in cutaneous biology, e.g. in proliferation and differentiation of epidermal keratinocytes and in cutaneous wound repair. Furthermore, the role of lncRNAs in keratinocyte-derived skin cancers is emerging, especially in ...
Source: Cellular and Molecular Life Sciences : CMLS - May 27, 2020 Category: Cytology Authors: Piipponen M, Nissinen L, Kähäri VM Tags: Cell Mol Life Sci Source Type: research

Heparanase, cell signaling, and viral infections.
Abstract Heparanase (HPSE) is a multifunctional protein endowed with many non-enzymatic functions and a unique enzymatic activity as an endo-β-D-glucuronidase. The latter allows it to serve as a key modulator of extracellular matrix (ECM) via a well-regulated cleavage of heparan sulfate side chains of proteoglycans at cell surfaces. The cleavage and associated changes at the ECM cause release of multiple signaling molecules with important cellular and pathological functions. New and emerging data suggest that both enzymatic as well as non-enzymatic functions of HPSE are important for health and illnesses incl...
Source: Cellular and Molecular Life Sciences : CMLS - May 27, 2020 Category: Cytology Authors: Koganti R, Suryawanshi R, Shukla D Tags: Cell Mol Life Sci Source Type: research

Programmed genome rearrangements in ciliates.
cki M Abstract Ciliates are a highly divergent group of unicellular eukaryotes with separate somatic and germline genomes found in distinct dimorphic nuclei. This characteristic feature is tightly linked to extremely laborious developmentally regulated genome rearrangements in the development of a new somatic genome/nuclei following sex. The transformation from germline to soma genome involves massive DNA elimination mediated by non-coding RNAs, chromosome fragmentation, as well as DNA amplification. In this review, we discuss the similarities and differences in the genome reorganization processes of the model cil...
Source: Cellular and Molecular Life Sciences : CMLS - May 27, 2020 Category: Cytology Authors: Rzeszutek I, Maurer-Alcalá XX, Nowacki M Tags: Cell Mol Life Sci Source Type: research

Ubiquitin chromatin remodelling after DNA damage is associated with the expression of key cancer genes and pathways.
Abstract Modification of the cancer-associated chromatin landscape in response to therapeutic DNA damage influences gene expression and contributes to cell fate. The central histone mark H2Bub1 results from addition of a single ubiquitin on lysine 120 of histone H2B and is an important regulator of gene expression. Following treatment with a platinum-based chemotherapeutic, there is a reduction in global levels of H2Bub1 accompanied by an increase in levels of the tumor suppressor p53. Although total H2Bub1 decreases following DNA damage, H2Bub1 is enriched downstream of transcription start sites of specific genes...
Source: Cellular and Molecular Life Sciences : CMLS - May 26, 2020 Category: Cytology Authors: Cole AJ, Dickson KA, Liddle C, Stirzaker C, Shah JS, Clifton-Bligh R, Marsh DJ Tags: Cell Mol Life Sci Source Type: research

The formin INF2 in disease: progress from 10  years of research.
The formin INF2 in disease: progress from 10 years of research. Cell Mol Life Sci. 2020 May 25;: Authors: Labat-de-Hoz L, Alonso MA Abstract Formins are a conserved family of proteins that primarily act to form linear polymers of actin. Despite their importance to the normal functioning of the cytoskeleton, for a long time, the only two formin genes known to be a genetic cause of human disorders were DIAPH1 and DIAPH3, whose mutation causes two distinct forms of hereditary deafness. In the last 10 years, however, the formin INF2 has emerged as an important target of mutations responsible for...
Source: Cellular and Molecular Life Sciences : CMLS - May 25, 2020 Category: Cytology Authors: Labat-de-Hoz L, Alonso MA Tags: Cell Mol Life Sci Source Type: research

Metabolism and growth adaptation to environmental conditions in Drosophila.
Abstract Organisms adapt to changing environments by adjusting their development, metabolism, and behavior to improve their chances of survival and reproduction. To achieve such flexibility, organisms must be able to sense and respond to changes in external environmental conditions and their internal state. Metabolic adaptation in response to altered nutrient availability is key to maintaining energy homeostasis and sustaining developmental growth. Furthermore, environmental variables exert major influences on growth and final adult body size in animals. This developmental plasticity depends on adaptive responses ...
Source: Cellular and Molecular Life Sciences : CMLS - May 24, 2020 Category: Cytology Authors: Koyama T, Texada MJ, Halberg KA, Rewitz K Tags: Cell Mol Life Sci Source Type: research

Regulation of the expression of the estrogen related receptors (ERRs).
Abstract Estrogen related receptors (ERRα, β and γ in mammals) are orphan members of the nuclear receptor superfamily acting as transcription factors. ERRs are expressed in several tissues and cells and they display various physiological and pathological functions, controlling, amongst others and depending on the receptor, bone homeostasis, energy metabolism, embryonic stem cell pluripotency, and cancer progression. In contrast to classical nuclear receptors, the activities of the ERRs are not controlled by a natural ligand. Regulation of their activities thus rely on other means such as post-tran...
Source: Cellular and Molecular Life Sciences : CMLS - May 24, 2020 Category: Cytology Authors: Crevet L, Vanacker JM Tags: Cell Mol Life Sci Source Type: research

Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus.
Abstract The membrane lipids diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers that can regulate membrane transport by recruiting proteins to the membrane and by altering biophysical membrane properties. DAG and PA are involved in the transport from the Golgi apparatus to endosomes, and we have here investigated whether changes in these lipids might be important for regulation of transport to the Golgi using the protein toxin ricin. Modulation of DAG and PA levels using DAG kinase (DGK) and phospholipase D (PLD) inhibitors gave a strong increase in retrograde ricin transport, but had ...
Source: Cellular and Molecular Life Sciences : CMLS - May 23, 2020 Category: Cytology Authors: Lingelem ABD, Kavaliauskiene S, Halsne R, Klokk TI, Surma MA, Klose C, Skotland T, Sandvig K Tags: Cell Mol Life Sci Source Type: research