Joseph Barden, Olivia Kosloski, Amir Jadidian, Mohammed Akaaboune
{"title":"Regulation of miR-206 in denervated and dystrophic muscles, and its effect on acetylcholine receptor clustering.","authors":"Joseph Barden, Olivia Kosloski, Amir Jadidian, Mohammed Akaaboune","doi":"10.1242/jcs.262303","DOIUrl":"10.1242/jcs.262303","url":null,"abstract":"<p><p>The muscle-specific microRNA miR-206 has recently emerged as a potential regulator of genes involved in the formation and regeneration of the neuromuscular junction (NMJ). This study investigated miR-206-3p (miR-206) expression in synaptic and non-synaptic regions of denervated mice and α-dystrobrevin (Dtna)-knockout mice, as well as its impact on the formation and/or maintenance of agrin-induced acetylcholine receptor (AChR) clusters. In denervated, Dtna-deficient and crushed muscles, miR-206 expression significantly increased compared to what was seen for innervated muscles. Although miR-206 expression was slightly elevated in the synaptic regions of innervated muscles, it was dramatically increased in non-synaptic areas of denervated muscles. miR-206 targets transcripts of essential NMJ proteins, such as Dtna, α-syntrophin (Snta1) and rapsyn, but not the AChRα subunit (encoded by Chrna1) or Lrp4 in innervated muscles. However, in denervated muscles, AChRα transcripts, which increased significantly, become a target of miR-206. Co-expression of miR-206 with rapsyn, Dtna and Snta1 in C2C12 myoblasts significantly reduced their protein levels, and overexpression of miR-206 in myotubes disrupted agrin-induced AChR clustering. These results indicate that miR-206 fine-tunes NMJ signaling proteins by regulating transcripts of various proteins with different localizations under normal and pathological conditions.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phase separation of microtubule-binding proteins - implications for neuronal function and disease.","authors":"Daisy Duan, Anthony J Koleske","doi":"10.1242/jcs.263470","DOIUrl":"10.1242/jcs.263470","url":null,"abstract":"<p><p>Protein liquid-liquid phase separation (LLPS) is driven by intrinsically disordered regions and multivalent binding domains, both of which are common features of diverse microtubule (MT) regulators. Many in vitro studies have dissected the mechanisms by which MT-binding proteins (MBPs) regulate MT nucleation, stabilization and dynamics, and investigated whether LLPS plays a role in these processes. However, more recent in vivo studies have focused on how MBP LLPS affects biological functions throughout neuronal development. Dysregulation of MBP LLPS can lead to formation of aggregates - an underlying feature in many neurodegenerative diseases - such as the tau neurofibrillary tangles present in Alzheimer's disease. In this Review, we highlight progress towards understanding the regulation of MT dynamics through the lens of phase separation of MBPs and associated cytoskeletal regulators, from both in vitro and in vivo studies. We also discuss how LLPS of MBPs regulates neuronal development and maintains homeostasis in mature neurons.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 24","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Complexity and self-organization in the evolution of cell polarization.","authors":"Marieke M Glazenburg, Liedewij Laan","doi":"10.1242/jcs.263699","DOIUrl":"https://doi.org/10.1242/jcs.263699","url":null,"abstract":"","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 23","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extracellular vesicles and nanoparticles at a glance.","authors":"Dennis K Jeppesen, Qin Zhang, Robert J Coffey","doi":"10.1242/jcs.260201","DOIUrl":"10.1242/jcs.260201","url":null,"abstract":"<p><p>Cells can communicate with neighboring and more distant cells by secretion of extracellular vesicles (EVs). EVs are lipid bilayer membrane-bound structures that can be packaged with proteins, nucleic acids and lipids that mediate cell-cell signaling. EVs are increasingly recognized to play numerous important roles in both normal physiological processes and pathological conditions. Steady progress in the field has uncovered a great diversity and heterogeneity of distinct vesicle types that appear to be secreted from most, if not all, cell types. Recently, it has become apparent that cells also release non-vesicular extracellular nanoparticles (NVEPs), including the newly discovered exomeres and supermeres. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of the diversity of EVs and nanoparticles that are released from cells into the extracellular space, highlighting recent advances in the field.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 23","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabienne De Graeve, Eric Debreuve, Kavya Vinayan Pushpalatha, Xuchun Zhang, Somia Rahmoun, Djampa Kozlowski, Nicolas Cedilnik, Jeshlee Vijayakumar, Paul Cassini, Sebastien Schaub, Xavier Descombes, Florence Besse
{"title":"An image-based RNAi screen identifies the EGFR signaling pathway as a regulator of Imp RNP granules.","authors":"Fabienne De Graeve, Eric Debreuve, Kavya Vinayan Pushpalatha, Xuchun Zhang, Somia Rahmoun, Djampa Kozlowski, Nicolas Cedilnik, Jeshlee Vijayakumar, Paul Cassini, Sebastien Schaub, Xavier Descombes, Florence Besse","doi":"10.1242/jcs.262119","DOIUrl":"10.1242/jcs.262119","url":null,"abstract":"<p><p>Biomolecular condensates have recently retained much attention given that they provide a fundamental mechanism of cellular organization. Among those, cytoplasmic ribonucleoprotein (RNP) granules selectively and reversibly concentrate RNA molecules and regulatory proteins, thus contributing to the spatiotemporal regulation of associated RNAs. Extensive in vitro work has unraveled the molecular and chemical bases of RNP granule assembly. The signaling pathways controlling this process in a cellular context are, however, still largely unknown. Here, we aimed at identifying regulators of cytoplasmic RNP granules characterized by the presence of the evolutionarily conserved Imp RNA-binding protein (a homolog of IGF2BP proteins). We performed a high-content image-based RNAi screen targeting all Drosophila genes encoding RNA-binding proteins, phosphatases and kinases. This led to the identification of dozens of genes regulating the number of Imp-positive RNP granules in S2R+ cells, among which were components of the MAPK pathway. Combining functional approaches, phospho-mapping and generation of phospho-variants, we further showed that EGFR signaling inhibits Imp-positive RNP granule assembly through activation of the MAPK-ERK pathway and downstream phosphorylation of Imp at the S15 residue. This work illustrates how signaling pathways can regulate cellular condensate assembly by post-translational modifications of specific components.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily D McParland, Noah J Gurley, Leah R Wolfsberg, T Amber Butcher, Abhi Bhattarai, Corbin C Jensen, Ruth I Johnson, Kevin C Slep, Mark Peifer
{"title":"The dual Ras-association domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis.","authors":"Emily D McParland, Noah J Gurley, Leah R Wolfsberg, T Amber Butcher, Abhi Bhattarai, Corbin C Jensen, Ruth I Johnson, Kevin C Slep, Mark Peifer","doi":"10.1242/jcs.263546","DOIUrl":"10.1242/jcs.263546","url":null,"abstract":"<p><p>During development cells must change shape and move without disrupting dynamic tissue architecture. This requires robust linkage of cell-cell adherens junctions to the force-generating actomyosin cytoskeleton. Drosophila Canoe and mammalian afadin play key roles in the regulation of such linkages. One central task for the field is defining mechanisms by which upstream inputs from Ras-family GTPases regulate Canoe and afadin. These proteins are unusual in sharing two tandem Ras-association (RA) domains - RA1 and RA2 - which when deleted virtually eliminate Canoe function. Work in vitro has suggested that RA1 and RA2 differ in GTPase affinity, but their individual functions in vivo remain unknown. Combining bioinformatic and biochemical approaches, we find that both RA1 and RA2 bind to active Rap1 with similar affinities, and that their conserved N-terminal extensions enhance binding. We created Drosophila canoe mutants to test RA1 and RA2 function in vivo. Despite their similar affinities for Rap1, RA1 and RA2 play strikingly different roles. Deleting RA1 virtually eliminates Canoe function, whereas mutants lacking RA2 are viable and fertile but have defects in junctional reinforcement in embryos and during pupal eye development. These data significantly expand our understanding of the regulation of adherens junction-cytoskeletal linkages.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikita Sergejevs, Dönem Avci, Michael L van de Weijer, Robin A Corey, Marius K Lemberg, Pedro Carvalho
{"title":"Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.","authors":"Nikita Sergejevs, Dönem Avci, Michael L van de Weijer, Robin A Corey, Marius K Lemberg, Pedro Carvalho","doi":"10.1242/jcs.262333","DOIUrl":"10.1242/jcs.262333","url":null,"abstract":"<p><p>Cleavage of transmembrane segments on target proteins by the aspartyl intramembrane protease signal peptide peptidase (SPP, encoded by HM13) has been linked to immunity, viral infection and protein quality control. How SPP recognizes its various substrates and specifies their fate remains elusive. Here, we identify the lanosterol demethylase CYP51A1 as an SPP substrate and show that SPP-catalysed cleavage triggers CYP51A1 clearance by endoplasmic reticulum-associated degradation (ERAD). We observe that SPP targets only a fraction of CYP51A1 molecules, and we identify an amphipathic helix in the CYP51A1 N terminus as a key determinant for SPP recognition. SPP recognition is remarkably specific to CYP51A1 molecules with the amphipathic helix aberrantly inserted in the membrane with a type II orientation. Thus, our data are consistent with a role for SPP in topology surveillance, triggering the clearance of certain potentially non-functional conformers.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inga Mohr, Monique Eutebach, Marie C Knopf, Naima Schommen, Regina Gratz, Kalina Angrand, Lara Genders, Tzvetina Brumbarova, Petra Bauer, Rumen Ivanov
{"title":"The small ARF-like 2 GTPase TITAN5 is linked with the dynamic regulation of IRON-REGULATED TRANSPORTER 1.","authors":"Inga Mohr, Monique Eutebach, Marie C Knopf, Naima Schommen, Regina Gratz, Kalina Angrand, Lara Genders, Tzvetina Brumbarova, Petra Bauer, Rumen Ivanov","doi":"10.1242/jcs.263645","DOIUrl":"10.1242/jcs.263645","url":null,"abstract":"<p><p>Iron acquisition is crucial for plants. The abundance of IRON-REGULATED TRANSPORTER 1 (IRT1) is controlled through endomembrane trafficking, a process that requires small ARF-like GTPases. Only few components that are involved in the vesicular trafficking of specific cargo are known. Here, we report that the ARF-like GTPase TITAN5 (TTN5) interacts with the large cytoplasmic variable region and protein-regulatory platform of IRT1. Heterozygous ttn5-1 plants can display reduced root iron reductase activity. This activity is needed for iron uptake via IRT1. Fluorescent fusion proteins of TTN5 and IRT1 colocalize at locations where IRT1 sorting and cycling between the plasma membrane and the vacuole are coordinated. TTN5 can also interact with peripheral membrane proteins that are components of the IRT1 regulation machinery, like the trafficking factor SNX1, the C2 domain protein EHB1 and the SEC14-GOLD protein PATL2. Hence, the link between iron acquisition and vesicular trafficking involving a small GTPase of the ARF family opens up the possibility to study the involvement of TTN5 in nutritional cell biology and the endomembrane system.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CAMSAP3 forms dimers via its α-helix domain that directly stabilize non-centrosomal microtubule minus ends.","authors":"Yuejia Li, Rui Zhang, Jinqi Ren, Wei Chen, Zhengrong Zhou, Honglin Xu, Dong Li, Haisu Cheng, Qi Xie, Wei Ji, Wei Feng, Xin Liang, Wenxiang Meng","doi":"10.1242/jcs.263609","DOIUrl":"10.1242/jcs.263609","url":null,"abstract":"<p><p>Microtubules are vital components of the cytoskeleton. Their plus ends are dynamic and respond to changes in cell morphology, whereas the minus ends are stable and serve a crucial role in microtubule seeding and maintaining spatial organization. In mammalian cells, the calmodulin-regulated spectrin-associated proteins (CAMSAPs), play a key role in directly regulating the dynamics of non-centrosomal microtubules minus ends. However, the molecular mechanisms are not yet fully understood. Our study reveals that CAMSAP3 forms dimers through its C-terminal α-helix; this dimerization not only enhances the microtubule-binding affinity of the CKK domain but also enables the CKK domain to regulate the dynamics of microtubules. Furthermore, CAMSAP3 also specializes in decorating at the minus end of microtubules through the combined action of the microtubule-binding domain (MBD) and the C-terminal α-helix, thereby achieving dynamic regulation of the minus ends of microtubules. These findings are crucial for advancing our understanding and treatment of diseases associated with non-centrosomal microtubules.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Cohen, Dawn Fernandez, Francisco Lázaro-Diéguez, Beatrix Überheide, Anne Müsch
{"title":"Borg5 restricts contractility and motility in epithelial MDCK cells.","authors":"David Cohen, Dawn Fernandez, Francisco Lázaro-Diéguez, Beatrix Überheide, Anne Müsch","doi":"10.1242/jcs.261705","DOIUrl":"10.1242/jcs.261705","url":null,"abstract":"<p><p>The Borg (or Cdc42EP) family consists of septin-binding proteins that are known to promote septin-dependent stress fibers and acto-myosin contractility. We show here that epithelial Borg5 (also known as Cdc42EP1) instead limits contractility, cell-cell adhesion tension and motility, as is required for the acquisition of columnar, isotropic cell morphology in mature MDCK monolayers. Borg5 depletion inhibited the development of the lateral F-actin cortex and stimulated microtubule-dependent leading-edge lamellae as well as radial stress fibers and, independently of the basal F-actin phenotype, caused anisotropy of apical surfaces within compacted monolayers. We determined that Borg5 limits colocalization of septin proteins with microtubules, and that like septin 2, Borg5 interacts with the rod-domain of myosin IIA (herein referring to the MYH9 heavy chain). The interaction of myosin IIA with Borg5 was reduced in the presence of septins. Because septins also mediate myosin activation, we propose that Borg5 limits contractility in MDCK cells in part by counteracting septin-associated myosin activity.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}