Folding and assembly defects of pyruvate dehydrogenase deficiency-related variants in the E1 α subunit of the pyruvate dehydrogenase complex.
Folding and assembly defects of pyruvate dehydrogenase deficiency-related variants in the E1α subunit of the pyruvate dehydrogenase complex. Cell Mol Life Sci. 2018 Feb 14;: Authors: Drakulic S, Rai J, Petersen SV, Golas MM, Sander B Abstract The pyruvate dehydrogenase complex (PDC) bridges glycolysis and the citric acid cycle. In human, PDC deficiency leads to severe neurodevelopmental delay and progressive neurodegeneration. The majority of cases are caused by variants in the gene encoding the PDC subunit E1α. The molecular effects of the variants, however, remain poorly understood. Usin...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2018 Category: Cytology Authors: Drakulic S, Rai J, Petersen SV, Golas MM, Sander B Tags: Cell Mol Life Sci Source Type: research

Conformational change of the extracellular parts of the CFTR protein during channel gating.
Abstract Cystic fibrosis can be treated by potentiators, drugs that interact directly with the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel to increase its open probability. These substances likely target key conformational changes occurring during channel opening and closing, however, the molecular bases of these conformational changes, and their susceptibility to manipulation are poorly understood. We have used patch clamp recording to identify changes in the three-dimensional organization of the extracellularly accessible parts of the CFTR protein during channel opening and closing. St...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2018 Category: Cytology Authors: Negoda A, Cowley EA, El Hiani Y, Linsdell P Tags: Cell Mol Life Sci Source Type: research

Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins.
This study shows that SEC alone is unable to completely separate plasma EVs from lipoprotein particles. However, combining SEC with a density cushion significantly improved the separation of EVs from lipoproteins and allowed for a detailed analysis of the proteome of plasma EVs, thus making blood a viable source for EV biomarker discovery. PMID: 29441425 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - February 13, 2018 Category: Cytology Authors: Karimi N, Cvjetkovic A, Jang SC, Crescitelli R, Hosseinpour Feizi MA, Nieuwland R, Lötvall J, Lässer C Tags: Cell Mol Life Sci Source Type: research

RIPK4 activity in keratinocytes is controlled by the SCF β-TrCP ubiquitin ligase to maintain cortical actin organization.
RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization. Cell Mol Life Sci. 2018 Feb 12;: Authors: Tanghe G, Urwyler-Rösselet C, De Groote P, Dejardin E, De Bock PJ, Gevaert K, Vandenabeele P, Declercq W Abstract RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-κB activation. However, the mechanism regulating RIPK4 activity levels re...
Source: Cellular and Molecular Life Sciences : CMLS - February 12, 2018 Category: Cytology Authors: Tanghe G, Urwyler-Rösselet C, De Groote P, Dejardin E, De Bock PJ, Gevaert K, Vandenabeele P, Declercq W Tags: Cell Mol Life Sci Source Type: research

An emerging link between LIM domain proteins and nuclear receptors.
Abstract Nuclear receptors are ligand-activated transcription factors that partake in several biological processes including development, reproduction and metabolism. Over the last decade, evidence has accumulated that group 2, 3 and 4 LIM domain proteins, primarily known for their roles in actin cytoskeleton organization, also partake in gene transcription regulation. They shuttle between the cytoplasm and the nucleus, amongst other as a consequence of triggering cells with ligands of nuclear receptors. LIM domain proteins act as important coregulators of nuclear receptor-mediated gene transcription, in which the...
Source: Cellular and Molecular Life Sciences : CMLS - February 10, 2018 Category: Cytology Authors: Sala S, Ampe C Tags: Cell Mol Life Sci Source Type: research

The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis.
The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis. Cell Mol Life Sci. 2018 Feb 10;: Authors: Warren NA, Voloudakis G, Yoon Y, Robakis NK, Georgakopoulos A Abstract Presenilin-1 (PS1) gene encodes the catalytic component of γ-secretase, which proteolytically processes several type I transmembrane proteins. We here present evidence that the cytosolic peptide efnB2/CTF2 produced by the PS1/γ-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro. EfnB2/CTF2 increases endothelial cell sprouting and t...
Source: Cellular and Molecular Life Sciences : CMLS - February 10, 2018 Category: Cytology Authors: Warren NA, Voloudakis G, Yoon Y, Robakis NK, Georgakopoulos A Tags: Cell Mol Life Sci Source Type: research

SLC52A3 expression is activated by NF- κB p65/Rel-B and serves as a prognostic biomarker in esophageal cancer.
In this study, we find that SLC52A3 has two transcript variants that differ in the transcriptional start site, and encode different proteins: SLC52A3a and SLC52A3b. Importantly, aberrant expressions of SLC52A3 are associated with stepwise development of esophageal squamous cell carcinoma (ESCC) as well as the survival rates of ESCC patients. Functionally, SLC52A3a, but not SLC52A3b, strongly promotes the proliferation and colony formation of ESCC cells. Furthermore, SLC52A3 5'-flanking regions contain NF-κB p65/Rel-B-binding sites, which are crucial for mediating SLC52A3 transcriptional activity in ESCC cells. Chroma...
Source: Cellular and Molecular Life Sciences : CMLS - February 10, 2018 Category: Cytology Authors: Long L, Pang XX, Lei F, Zhang JS, Wang W, Liao LD, Xu XE, He JZ, Wu JY, Wu ZY, Wang LD, Lin DC, Li EM, Xu LY Tags: Cell Mol Life Sci Source Type: research

Dissecting the biochemical architecture and morphological release pathways of the human platelet extracellular vesiculome.
Abstract Platelet extracellular vesicles (PEVs) have emerged as potential mediators in intercellular communication. PEVs exhibit several activities with pathophysiological importance and may serve as diagnostic biomarkers. Here, imaging and analytical techniques were employed to unveil morphological pathways of the release, structure, composition, and surface properties of PEVs derived from human platelets (PLTs) activated with the thrombin receptor activating peptide (TRAP). Based on extensive electron microscopy analysis, we propose four morphological pathways for PEVs release from TRAP-activated PLTs: (1) plasm...
Source: Cellular and Molecular Life Sciences : CMLS - February 9, 2018 Category: Cytology Authors: De Paoli SH, Tegegn TZ, Elhelu OK, Strader MB, Patel M, Diduch LL, Tarandovskiy ID, Wu Y, Zheng J, Ovanesov MV, Alayash A, Simak J Tags: Cell Mol Life Sci Source Type: research

Lipids in the cell: organisation regulates function.
Abstract Lipids are fundamental building blocks of all cells and play important roles in the pathogenesis of different diseases, including inflammation, autoimmune disease, cancer, and neurodegeneration. The lipid composition of different organelles can vary substantially from cell to cell, but increasing evidence demonstrates that lipids become organised specifically in each compartment, and this organisation is essential for regulating cell function. For example, lipid microdomains in the plasma membrane, known as lipid rafts, are platforms for concentrating protein receptors and can influence intra-cellular sig...
Source: Cellular and Molecular Life Sciences : CMLS - February 9, 2018 Category: Cytology Authors: Santos AL, Preta G Tags: Cell Mol Life Sci Source Type: research

Autophagy as a target for glucocorticoid-induced osteoporosis therapy.
Abstract Autophagy takes part in regulating the eukaryotic cells function and the progression of numerous diseases, but its clinical utility has not been fully developed yet. Recently, mounting evidences highlight an important correlation between autophagy and bone homeostasis, mediated by osteoclasts, osteocytes, bone marrow mesenchymal stem cells, and osteoblasts, and autophagy plays a vital role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). The combinations of autophagy activators/inhibitors with anti-GIOP first-line drugs or some new autophagy-based manipulators, such as regulation of B ce...
Source: Cellular and Molecular Life Sciences : CMLS - February 9, 2018 Category: Cytology Authors: Shen G, Ren H, Shang Q, Qiu T, Yu X, Zhang Z, Huang J, Zhao W, Zhang Y, Liang, Jiang X Tags: Cell Mol Life Sci Source Type: research

Giant fish-killing water bug reveals ancient and dynamic venom evolution in Heteroptera.
We report 132 venom proteins including putative enzymes, cytolytic toxins, and antimicrobial peptides. Over 73% (96 proteins) showed homology to venom proteins from assassin bugs (Reduviidae), including 21% (28 proteins from seven families) not known from other sources. These data suggest that numerous protein families were recruited into venom and diversified rapidly following the switch from phytophagy to predation by ancestral heteropterans, and then were retained over > 200 my of evolution. In contrast, trophic switches to blood-feeding (e.g. in Triatominae and Cimicidae) or reversions to plant-f...
Source: Cellular and Molecular Life Sciences : CMLS - February 9, 2018 Category: Cytology Authors: Walker AA, Hernández-Vargas MJ, Corzo G, Fry BG, King GF Tags: Cell Mol Life Sci Source Type: research

Post-translational regulation of the maternal-to-zygotic transition.
Abstract The maternal-to-zygotic transition (MZT) is essential for the developmental control handed from maternal products to newly synthesized zygotic genome in the earliest stages of embryogenesis, including maternal component (mRNAs and proteins) degradation and zygotic genome activation (ZGA). Various protein post-translational modifications have been identified during the MZT, such as phosphorylation, methylation and ubiquitination. Precise post-translational regulation mechanisms are essential for the timely transition of early embryonic development. In this review, we summarize recent progress regarding the...
Source: Cellular and Molecular Life Sciences : CMLS - February 9, 2018 Category: Cytology Authors: Liu C, Ma Y, Shang Y, Huo R, Li W Tags: Cell Mol Life Sci Source Type: research

Cellular functions of stem cell factors mediated by the ubiquitin-proteasome system.
Abstract Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin-proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery. The UPS controls cell development, survival, differentiation, lineage commitment, mi...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2018 Category: Cytology Authors: Choi J, Baek KH Tags: Cell Mol Life Sci Source Type: research

Structure and function of Zika virus NS5 protein: perspectives for drug design.
Abstract Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure-function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of hos...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2018 Category: Cytology Authors: Wang B, Thurmond S, Hai R, Song J Tags: Cell Mol Life Sci Source Type: research

Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.
Abstract Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process for the clearance of damaged or superfluous proteins and organelles. Accumulating studies have recently revealed that autophagy is closely related to a variety of types of cancer; however, elucidation of its Janus role of either tumor-suppressive or tumor-promoting still remains to be discovered. In this review, we focus on summarizing the context-dependent role of autophagy and its complicated molecular mechanisms in different types of cancer. Moreover, we discuss a series of small-molecule compounds targeting autophagy-re...
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2018 Category: Cytology Authors: Zhang J, Wang G, Zhou Y, Chen Y, Ouyang L, Liu B Tags: Cell Mol Life Sci Source Type: research

Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion.
Abstract Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with ...
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2018 Category: Cytology Authors: De Berdt P, Bottemanne P, Bianco J, Alhouayek M, Diogenes A, Llyod A, Gerardo-Nava J, Brook GA, Miron V, Muccioli GG, Rieux AD Tags: Cell Mol Life Sci Source Type: research

Cellular and molecular mechanisms of HIV-1 integration targeting.
Abstract Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to prin...
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2018 Category: Cytology Authors: Engelman AN, Singh PK Tags: Cell Mol Life Sci Source Type: research

The DNA double-strand "breakome" of mouse spermatids.
The DNA double-strand "breakome" of mouse spermatids. Cell Mol Life Sci. 2018 Feb 07;: Authors: Grégoire MC, Leduc F, Morin MH, Cavé T, Arguin M, Richter M, Jacques PÉ, Boissonneault G Abstract De novo germline mutations arise preferentially in male owing to fundamental differences between spermatogenesis and oogenesis. Post-meiotic chromatin remodeling in spermatids results in the elimination of most of the nucleosomal supercoiling and is characterized by transient DNA fragmentation. Using three alternative methods, DNA from sorted populations of mouse spermatids was us...
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2018 Category: Cytology Authors: Grégoire MC, Leduc F, Morin MH, Cavé T, Arguin M, Richter M, Jacques PÉ, Boissonneault G Tags: Cell Mol Life Sci Source Type: research

Cystic fibrosis transmembrane conductance regulator-emerging regulator of cancer.
Abstract Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR wit...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2018 Category: Cytology Authors: Zhang J, Wang Y, Jiang X, Chan HC Tags: Cell Mol Life Sci Source Type: research

Nanos genes and their role in development and beyond.
Abstract The hallmark of Nanos proteins is their typical (CCHC)2 zinc finger motif (zf-nanos). Animals have one to four nanos genes. For example, the fruit fly and demosponge have only one nanos gene, zebrafish and humans have three, and Fugu rubripes has four. Nanos genes are mainly known for their evolutionarily preserved role in germ cell survival and pluripotency. Nanos proteins have been reported to bind the C-terminal RNA-binding domain of Pumilio to form a post-transcriptional repressor complex. Several observations point to a link between the miRNA-mediated repression complex and the Nanos/Pumilio complex....
Source: Cellular and Molecular Life Sciences : CMLS - February 3, 2018 Category: Cytology Authors: De Keuckelaere E, Hulpiau P, Saeys Y, Berx G, van Roy F Tags: Cell Mol Life Sci Source Type: research

Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles.
Abstract Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of th...
Source: Cellular and Molecular Life Sciences : CMLS - February 3, 2018 Category: Cytology Authors: Singh SK, Pandey H, Al-Bassam J, Gheber L Tags: Cell Mol Life Sci Source Type: research

TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms.
er LB Abstract Primary cilia are sensory organelles that coordinate multiple cellular signaling pathways, including Hedgehog (HH), Wingless/Int (WNT) and Transforming Growth Factor-β (TGF-β) signaling. Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Complex proteins 1 and 2 (TSC1/2) negatively regulate protein synthesis by inactivating the mTOR complex 1 (mTORC1) at energy limiting states. Here we report that TSC1 and TSC2 regulate Smoothened (SMO)-dependent HH signaling in mouse embryonic fibroblasts (MEFs). Reduced SMO-dependent expression of G...
Source: Cellular and Molecular Life Sciences : CMLS - February 2, 2018 Category: Cytology Authors: Rosengren T, Larsen LJ, Pedersen LB, Christensen ST, Møller LB Tags: Cell Mol Life Sci Source Type: research

Lnc-ing non-coding RNAs with metabolism and diabetes: roles of lncRNAs.
Abstract Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and pancreatic β-cell dysfunction. Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with this disease and its complications. Long non-coding RNAs (lncRNAs) are a novel class of functional RNAs that regulate a variety of biological processes by a diverse interplay of mechanisms including recruitment of epigenetic modifiers, transcriptional and post-transcriptional regulation, control of mRNA decay, and sequestration of transcription factors. Although the underlying causes th...
Source: Cellular and Molecular Life Sciences : CMLS - January 31, 2018 Category: Cytology Authors: Goyal N, Kesharwani D, Datta M Tags: Cell Mol Life Sci Source Type: research

Structure and dynamics of rotary V1 motor.
Abstract Rotary ATPases are unique rotary molecular motors that function as energy conversion machines. Among all known rotary ATPases, F1-ATPase is the best characterized rotary molecular motor. There are many high-resolution crystal structures and the rotation dynamics have been investigated in detail by extensive single-molecule studies. In contrast, knowledge on the structure and rotation dynamics of V1-ATPase, another rotary ATPase, has been limited. However, recent high-resolution structural studies and single-molecule studies on V1-ATPase have provided new insights on how the catalytic sites in this molecul...
Source: Cellular and Molecular Life Sciences : CMLS - January 31, 2018 Category: Cytology Authors: Ueno H, Suzuki K, Murata T Tags: Cell Mol Life Sci Source Type: research

Retinoic acid signaling and neurogenic niche regulation in the developing peripheral nervous system of the cephalochordate amphioxus.
This study assesses the requirement of RA signaling for establishing a functional PNS in the cephalochordate amphioxus, the best available stand-in for the ancestral chordate condition. Pharmacological manipulation of RA signaling levels during embryogenesis reduces the ability of amphioxus larvae to respond to sensory stimulation and alters the number and distribution of ectodermal sensory neurons (ESNs) in a stage- and context-dependent manner. Using gene expression assays combined with immunohistochemistry, we show that this is because RA signaling specifically acts on a small population of soxb1c-expressing ESN progeni...
Source: Cellular and Molecular Life Sciences : CMLS - January 31, 2018 Category: Cytology Authors: Zieger E, Garbarino G, Robert NSM, Yu JK, Croce JC, Candiani S, Schubert M Tags: Cell Mol Life Sci Source Type: research

Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing.
We report that phospholipase D3 (PLD3), a type II membrane protein, functions in endosomal protein sorting and plays an important role in regulating APP processing. PLD3 co-localises with APP in endosomes and loss of PLD3 function results in reduced endosomal tubules, impaired trafficking of several membrane proteins and reduced association of sortilin-like 1 with APP. PMID: 29368044 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 24, 2018 Category: Cytology Authors: Mukadam AS, Breusegem SY, Seaman MNJ Tags: Cell Mol Life Sci Source Type: research

Tumor suppressor C-RASSF proteins.
Abstract Human genome has ten genes that are collectedly called Ras association domain family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N-RASSF and C-RASSF encode Ras association domain-containing proteins and are frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF and N-RASSF are quite different. Six C-RASSF proteins (RASSF1-6) are characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo domain, while four N-RASSF proteins (RASSF7-10) lack it. C-RASSF proteins interact with mammalian Ste20-like kinases-the core kinases of the tumor suppr...
Source: Cellular and Molecular Life Sciences : CMLS - January 20, 2018 Category: Cytology Authors: Iwasa H, Hossain S, Hata Y Tags: Cell Mol Life Sci Source Type: research

HBeAg induces the expression of macrophage miR-155 to accelerate liver injury via promoting production of inflammatory cytokines.
In conclusion, our data revealed that HBeAg augments the expression of miR-155 in macrophages via PI3K and NF-κB signal pathway and the increased miR-155 promotes HBeAg-induced inflammatory cytokine production by inhibiting the expression of BCL-6, SHIP-1, and SOCS-1. PMID: 29349567 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 18, 2018 Category: Cytology Authors: Wang W, Bian H, Li F, Li X, Zhang D, Sun S, Song S, Zhu Q, Ren W, Qin C, Qi J Tags: Cell Mol Life Sci Source Type: research

VRK1 and AURKB form a complex that cross inhibit their kinase activity and the phosphorylation of histone H3 in the progression of mitosis.
zo PA Abstract Regulation of cell division requires the integration of signals implicated in chromatin reorganization and coordination of its sequential changes in mitosis. Vaccinia-related kinase 1 (VRK1) and Aurora B (AURKB) are two nuclear kinases involved in different steps of cell division. We have studied whether there is any functional connection between these two nuclear kinases, which phosphorylate histone H3 in Thr3 and Ser10, respectively. VRK1 and AURKB are able to form a stable protein complex, which represents only a minor subpopulation of each kinase within the cell and is detected following nocodaz...
Source: Cellular and Molecular Life Sciences : CMLS - January 16, 2018 Category: Cytology Authors: Moura DS, Campillo-Marcos I, Vázquez-Cedeira M, Lazo PA Tags: Cell Mol Life Sci Source Type: research

Molecular recognition of microbial lipid-based antigens by T cells.
Abstract The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells...
Source: Cellular and Molecular Life Sciences : CMLS - January 16, 2018 Category: Cytology Authors: Gras S, Van Rhijn I, Shahine A, Le Nours J Tags: Cell Mol Life Sci Source Type: research

Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming.
Abstract The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite 'two-in-one' DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the mole...
Source: Cellular and Molecular Life Sciences : CMLS - January 15, 2018 Category: Cytology Authors: Malik V, Zimmer D, Jauch R Tags: Cell Mol Life Sci Source Type: research

Structural insights into the function of Elongator.
Abstract Conserved from yeast to humans, Elongator is a protein complex implicated in multiple processes including transcription regulation, α-tubulin acetylation, and tRNA modification, and its defects have been shown to cause human diseases such as familial dysautonomia. Elongator consists of two copies of six core subunits (Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6) that are organized into two subcomplexes: Elp1/2/3 and Elp4/5/6 and form a stable assembly of ~ 850 kDa in size. Although the catalytic subunit of Elongator is Elp3, which contains a radical S-adenosyl-L-methionine (SAM) domain and...
Source: Cellular and Molecular Life Sciences : CMLS - January 13, 2018 Category: Cytology Authors: Dalwadi U, Yip CK Tags: Cell Mol Life Sci Source Type: research

Reprogramming the metabolome rescues retinal degeneration.
Abstract Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal me...
Source: Cellular and Molecular Life Sciences : CMLS - January 13, 2018 Category: Cytology Authors: Park KS, Xu CL, Cui X, Tsang SH Tags: Cell Mol Life Sci Source Type: research

The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?
eth J Abstract Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell's major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system p...
Source: Cellular and Molecular Life Sciences : CMLS - January 11, 2018 Category: Cytology Authors: Tinkov AA, Bjørklund G, Skalny AV, Holmgren A, Skalnaya MG, Chirumbolo S, Aaseth J Tags: Cell Mol Life Sci Source Type: research

Molecular function of the novel α7β2 nicotinic receptor.
Molecular function of the novel α7β2 nicotinic receptor. Cell Mol Life Sci. 2018 Jan 08;: Authors: Nielsen BE, Minguez T, Bermudez I, Bouzat C Abstract The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Receptors containing up t...
Source: Cellular and Molecular Life Sciences : CMLS - January 8, 2018 Category: Cytology Authors: Nielsen BE, Minguez T, Bermudez I, Bouzat C Tags: Cell Mol Life Sci Source Type: research

An MD2-derived peptide promotes LPS aggregation, facilitates its internalization in THP-1 cells, and inhibits LPS-induced pro-inflammatory responses.
Abstract MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. A 16-residue stretch (MD54) from MD2 protein has been identified that possesses a short heptad repeat sequence and four cationic residues enabling ...
Source: Cellular and Molecular Life Sciences : CMLS - January 8, 2018 Category: Cytology Authors: Tandon A, Harioudh MK, Ishrat N, Tripathi AK, Srivastava S, Ghosh JK Tags: Cell Mol Life Sci Source Type: research

Therapeutic approaches for induction of tolerance and immune quiescence in corneal allotransplantation.
Abstract The cornea is the most commonly transplanted tissue in the body. Corneal grafts in low-risk recipients enjoy high success rates, yet over 50% of high-risk grafts (with inflamed and vascularized host beds) are rejected. As our understanding of the cellular and molecular pathways that mediate rejection has deepened, a number of novel therapeutic strategies have been unveiled. This manuscript reviews therapeutic approaches to promote corneal transplant survival through targeting (1) corneal lymphangiogenesis and hemangiogenesis, (2) antigen presenting cells, (3) effector and regulatory T cells, and (4) mesen...
Source: Cellular and Molecular Life Sciences : CMLS - January 6, 2018 Category: Cytology Authors: Tahvildari M, Amouzegar A, Foulsham W, Dana R Tags: Cell Mol Life Sci Source Type: research

Primary cilia proteins: ciliary and extraciliary sites and functions.
Abstract Primary cilia are immotile organelles known for their roles in development and cell signaling. Defects in primary cilia result in a range of disorders named ciliopathies. Because this organelle can be found singularly on almost all cell types, its importance extends to most organ systems. As such, elucidating the importance of the primary cilium has attracted researchers from all biological disciplines. As the primary cilia field expands, caution is warranted in attributing biological defects solely to the function of this organelle, since many of these "ciliary" proteins are found at other site...
Source: Cellular and Molecular Life Sciences : CMLS - January 5, 2018 Category: Cytology Authors: Hua K, Ferland RJ Tags: Cell Mol Life Sci Source Type: research

Inhibitors of protein translocation across membranes of the secretory pathway: novel antimicrobial and anticancer agents.
Abstract Proteins routed to the secretory pathway start their journey by being transported across biological membranes, such as the endoplasmic reticulum. The essential nature of this protein translocation process has led to the evolution of several factors that specifically target the translocon and block translocation. In this review, various translocation pathways are discussed together with known inhibitors of translocation. Properties of signal peptide-specific systems are highlighted for the development of new therapeutic and antimicrobial applications, as compounds can target signal peptides from either hos...
Source: Cellular and Molecular Life Sciences : CMLS - January 5, 2018 Category: Cytology Authors: Van Puyenbroeck V, Vermeire K Tags: Cell Mol Life Sci Source Type: research

Structure and function of the Nppa-Nppb cluster locus during heart development and disease.
Abstract Atrial natriuretic factor and brain natriuretic peptide are two important biomarkers in clinical cardiology. These two natriuretic peptide hormones are encoded by the paralogous genes Nppa and Nppb, which are evolutionary conserved. Both genes are predominantly expressed by the heart muscle during the embryonic and fetal stages, and in particular Nppa expression is strongly reduced in the ventricles after birth. Upon cardiac stress, Nppa and Nppb are strongly upregulated in the ventricular myocardium. Much is known about the molecular and physiological ques inducing Nppa and Nppb expression; however, the ...
Source: Cellular and Molecular Life Sciences : CMLS - January 4, 2018 Category: Cytology Authors: Man J, Barnett P, Christoffels VM Tags: Cell Mol Life Sci Source Type: research

Furin promotes dendritic morphogenesis and learning and memory in transgenic mice.
Abstract Furin is a proprotein convertase implicated in a variety of pathological processes including neurodegenerative diseases. However, the role of furin in neuronal plasticity and learning and memory remains to be elucidated. Here, we report that in brain-specific furin transgenic (Furin-Tg) mice, the dendritic spine density and proliferation of neural progenitor cells were significantly increased. These mice exhibited enhanced long-term potentiation (LTP) and spatial learning and memory performance, without alterations of miniature excitatory/inhibitory postsynaptic currents. In the cortex and hippocampus of ...
Source: Cellular and Molecular Life Sciences : CMLS - January 4, 2018 Category: Cytology Authors: Zhu B, Zhao L, Luo D, Xu D, Tan T, Dong Z, Tang Y, Min Z, Deng X, Sun F, Yan Z, Chen G Tags: Cell Mol Life Sci Source Type: research

Tight co-twin similarity of monozygotic twins for hTERT protein level of T cell subsets, for telomere length and mitochondrial DNA copy number, but not for telomerase activity.
oki DL, Bikov A, Molnár MJ, Buzás EI, Falus A Abstract Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals. Twin data of telomerase activity (...
Source: Cellular and Molecular Life Sciences : CMLS - December 30, 2017 Category: Cytology Authors: Melicher D, Illés A, Pállinger É, Kovács ÁF, Littvay L, Tárnoki ÁD, Tárnoki DL, Bikov A, Molnár MJ, Buzás EI, Falus A Tags: Cell Mol Life Sci Source Type: research

Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level.
iebermann H Abstract G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and relea...
Source: Cellular and Molecular Life Sciences : CMLS - December 30, 2017 Category: Cytology Authors: Fischer J, Kleinau G, Rutz C, Zwanziger D, Khajavi N, Müller A, Rehders M, Brix K, Worth CL, Führer D, Krude H, Wiesner B, Schülein R, Biebermann H Tags: Cell Mol Life Sci Source Type: research

Delta opioid receptors recycle to the membrane after sorting to the degradation path.
Abstract Soon after internalization delta opioid receptors (DOPrs) are committed to the degradation path by G protein-coupled receptor (GPCR)-associated binding protein. Here we provide evidence that this classical post-endocytic itinerary may be rectified by downstream sorting decisions which allow DOPrs to regain to the membrane after having reached late endosomes (LE). The LE sorting mechanism involved ESCRT accessory protein Alix and the TIP47/Rab9 retrieval complex which supported translocation of the receptor to the TGN, from where it subsequently regained the cell membrane. Preventing DOPrs from completing ...
Source: Cellular and Molecular Life Sciences : CMLS - December 29, 2017 Category: Cytology Authors: Charfi I, Abdallah K, Gendron L, Pineyro G Tags: Cell Mol Life Sci Source Type: research

Bacterial LPX motif-harboring virulence factors constitute a species-spanning family of cell-penetrating effectors.
In this study, we provide further evidence for the general concept of T3SS-independent translocation by identifying novel cell-penetrating features of these LPX effectors revealing an abundant species-spanning family of CPE. PMID: 29285573 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - December 28, 2017 Category: Cytology Authors: Norkowski S, Körner B, Greune L, Stolle AS, Lubos ML, Hardwidge PR, Schmidt MA, Rüter C Tags: Cell Mol Life Sci Source Type: research

Clostridium difficile-related postinfectious IBS: a case of enteroglial microbiological stalking and/or the solution of a conundrum?
Abstract Post-infectious irritable bowel syndrome is a well-defined pathological entity that develops in about one-third of subjects after an acute infection (bacterial, viral) or parasitic infestation. Only recently it has been documented that an high incidence of post-infectious irritable bowel syndrome occurs after Clostridium difficile infection. However, until now it is not known why in some patients recovered from this infection the gastrointestinal disturbances persist for months or years. Based on our in vitro studies on enteric glial cells exposed to the effects of C. difficile&nb...
Source: Cellular and Molecular Life Sciences : CMLS - December 28, 2017 Category: Cytology Authors: Bassotti G, Macchioni L, Corazzi L, Marconi P, Fettucciari K Tags: Cell Mol Life Sci Source Type: research

Identification of a novel lncRNA induced by the nephrotoxin ochratoxin A and expressed in human renal tumor tissue.
e M Abstract Long non-coding RNAs represent a fraction of the transcriptome that is being increasingly recognized. For most of them no function has been allocated so far. Here, we describe the nature and function of a novel non-protein-coding transcript, named WISP1-AS1, discovered in human renal proximal tubule cells exposed to the carcinogenic nephrotoxin ochratoxin A. WISP1-AS1 overlaps parts of the fourth intron and fifth exon of the Wnt1-inducible signaling pathway protein 1 (WISP1) gene. The transcript is 2922 nucleotides long, transcribed in antisense direction and predominantly localized in the nucleus. WI...
Source: Cellular and Molecular Life Sciences : CMLS - December 27, 2017 Category: Cytology Authors: Polovic M, Dittmar S, Hennemeier I, Humpf HU, Seliger B, Fornara P, Theil G, Azinovic P, Nolze A, Köhn M, Schwerdt G, Gekle M Tags: Cell Mol Life Sci Source Type: research

Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson's disease.
Abstract Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. The present study reveals that a single intracerebroventricular injection of 10 ng ODN 1 h after the last administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented the degeneration of DA neu...
Source: Cellular and Molecular Life Sciences : CMLS - December 20, 2017 Category: Cytology Authors: Bahdoudi S, Ghouili I, Hmiden M, do Rego JL, Lefranc B, Leprince J, Chuquet J, do Rego JC, Marcher AB, Mandrup S, Vaudry H, Tonon MC, Amri M, Masmoudi-Kouki O, Vaudry D Tags: Cell Mol Life Sci Source Type: research

Junctional adhesion molecule-A: functional diversity through molecular promiscuity.
Abstract Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell-cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Nevertheless, JAM-A is involved in a variety of biological processes. The functional diversity of JAM-A resides to a large part in a C-terminal PDZ domain binding motif which directly interacts with nine differe...
Source: Cellular and Molecular Life Sciences : CMLS - December 14, 2017 Category: Cytology Authors: Steinbacher T, Kummer D, Ebnet K Tags: Cell Mol Life Sci Source Type: research

iPSCs-based generation of vascular cells: reprogramming approaches and applications.
Abstract Recent advances in the field of induced pluripotent stem cells (iPSCs) research have opened a new avenue for stem cell-based generation of vascular cells. Based on their growth and differentiation potential, human iPSCs constitute a well-characterized, generally unlimited cell source for the mass generation of lineage- and patient-specific vascular cells without any ethical concerns. Human iPSCs-derived vascular cells are perfectly suited for vascular disease modeling studies because patient-derived iPSCs possess the disease-causing mutation, which might be decisive for full expression of the disease phen...
Source: Cellular and Molecular Life Sciences : CMLS - December 14, 2017 Category: Cytology Authors: Klein D Tags: Cell Mol Life Sci Source Type: research