Rachel Shannon,Yadu Balachandran,Xindi Wang,Maxime Boutry,Hong Xie,Peter K Kim,William S Trimble
{"title":"SEPTIN9 locally activates the RhoGEF ARHGEF18 to promote early stages of mitochondrial fission.","authors":"Rachel Shannon,Yadu Balachandran,Xindi Wang,Maxime Boutry,Hong Xie,Peter K Kim,William S Trimble","doi":"10.1083/jcb.202406017","DOIUrl":"https://doi.org/10.1083/jcb.202406017","url":null,"abstract":"Mitochondria continually undergo fission to maintain their network and health. Nascent fission sites are marked by the ER, which facilitates actin polymerization to drive calcium flux into the mitochondrion and constrict the inner mitochondrial membrane. Septins are a major eukaryotic cytoskeleton component that forms filaments that can both directly and indirectly modulate other cytoskeleton components, including actin. Septins have been implicated in mitochondrial fission; however, a connection between septins and the regulation of cytoskeletal machinery driving fission is not known. We find that SEPTIN9 is present at mitochondrial fission sites from its early stages with the ER and prior to the fission factor dynamin-related protein 1 (DRP1). SEPTIN9 has an isoform-specific role in fission, dependent on its N-terminal interaction to activate a Rho guanine nucleotide exchange factor, ARHGEF18. Without SEPTIN9, mitochondrial calcium influx is impaired, indicating SEPTIN9-containing octamers play a critical role in the early stages of fission.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"38 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anbang Dai, Peng Xu, Chase Amos, Kenshiro Fujise, Yumei Wu, Han Yang, Julia N Eisen, Andrés Guillén-Samander, Pietro De Camilli
{"title":"Multiple interactions recruit BLTP2 to ER-PM contacts to control plasma membrane dynamics.","authors":"Anbang Dai, Peng Xu, Chase Amos, Kenshiro Fujise, Yumei Wu, Han Yang, Julia N Eisen, Andrés Guillén-Samander, Pietro De Camilli","doi":"10.1083/jcb.202504027","DOIUrl":"10.1083/jcb.202504027","url":null,"abstract":"<p><p>BLTP2/KIAA0100, a bridge-like lipid transfer protein, was reported to localize at contacts of the ER with either the plasma membrane (PM) or recycling tubular endosomes depending on the cell type. Our findings suggest that mediating bulk lipid transport between the ER and the PM is a key function of this protein, as BLTP2 tethers the ER to tubular endosomes only after they become continuous with the PM and that it also tethers the ER to macropinosomes in the process of fusing with the PM. We further identify interactions underlying binding of BLTP2 to the PM, including phosphoinositides, the adaptor proteins FAM102A/FAM102B, and N-BAR domain proteins at membrane-connected tubules. The absence of BLTP2 results in the accumulation of intracellular vacuoles, many of which are connected to the PM, pointing to a role of the lipid transport function of BLTP2 in the control of PM dynamics.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 11","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonmuscle myosin II regulates presynaptic actin and neuronal mechanobiology in Drosophila.","authors":"Biljana Ermanoska, Jonathan Baets, Avital A Rodal","doi":"10.1083/jcb.202501211","DOIUrl":"10.1083/jcb.202501211","url":null,"abstract":"<p><p>Neuromuscular junctions (NMJs) are evolutionarily ancient, specialized contacts between neurons and muscles. They experience lifelong strain, yet the mechanism preserving their integrity under mechanical load remains unclear. Here, we identify a novel actomyosin structure at Drosophila larval NMJs, consisting of a long-lived, low-turnover presynaptic actin core that colocalizes with nonmuscle myosin II (NMII) and becomes disorganized upon manipulating neuronal NMII levels or activity. Intriguingly, neuronal NMII depletion altered postsynaptic NMII levels and organization near synapses, suggesting transsynaptic propagation of actomyosin rearrangements. Under these conditions, integrin adhesion receptors were reduced on both sides of the synapse, indicating disrupted neuron-muscle connections. Notably, axon severing mimics these effects, while axonal stretching reorganizes integrins without disrupting the actin core, suggesting that presynaptic actomyosin and integrin organization are highly sensitive to mechanical cues and dynamically adjust to both loss and gain of tension. Our study reveals a presynaptic actomyosin assembly that maintains mechanical continuity between neurons and muscle, potentially enabling mechanotransduction at the NMJ through integrin-mediated adhesion.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms of genome instability from cellular folate stress.","authors":"Christopher Mellor, Elisabeth A Larson, Meng Wang","doi":"10.1083/jcb.202502205","DOIUrl":"10.1083/jcb.202502205","url":null,"abstract":"<p><p>Folate is the key cofactor in one-carbon metabolism, a universal metabolic pathway crucial for supporting the biosynthesis of nucleotides, several amino acids, and key redox regulators. Mammals are unable to synthesize folate de novo, and folate deficiency can result from several causes, including restricted dietary intake, genetic defects in folate absorption and its metabolism, and exposure to antimetabolite drugs. The link between depletion of folates and genetic instability has long been the subject of research and is implicated in the pathogenesis of human diseases associated with folate deficiency. In this review, we will discuss the different genotoxic mechanisms arising from folate deficiency and the impact on genome stability. Increasing our understanding of this topic is crucial for interpreting possible links between genetic instability downstream of folate stress and the healthcare impact of folate deficiency.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"When huffing and puffing Ca2+ goes global, breast cancer cells are unmoved.","authors":"Woo Young Chung, Shmuel Muallem","doi":"10.1083/jcb.202507062","DOIUrl":"10.1083/jcb.202507062","url":null,"abstract":"<p><p>In this issue, Militsin et al. (https://doi.org/10.1083/jcb.202411203) reveal how STIM1 and STIM2-beyond their typical role as ER Ca2+ sensors that activate Orai1-control IP3R-mediated Ca2+ dynamics, thereby regulating breast cancer cell migration and invasion.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vanessa Teixeira, Kashish Singh, José B Gama, Matilde Moreira, Ricardo Celestino, Ana Xavier Carvalho, Paulo S Pereira, Carla M C Abreu, Tiago J Dantas, Andrew P Carter, Reto Gassmann
{"title":"CDR2 is a dynein adaptor recruited by kinectin to regulate ER sheet organization.","authors":"Vanessa Teixeira, Kashish Singh, José B Gama, Matilde Moreira, Ricardo Celestino, Ana Xavier Carvalho, Paulo S Pereira, Carla M C Abreu, Tiago J Dantas, Andrew P Carter, Reto Gassmann","doi":"10.1083/jcb.202411034","DOIUrl":"10.1083/jcb.202411034","url":null,"abstract":"<p><p>The ER relies on the microtubule cytoskeleton for the organization of its extended membrane network, but how microtubule-based motors contribute remains unclear. Using biochemical and cell-based assays, we identify cerebellar degeneration-related protein 2 (CDR2) and its paralog CDR2-like (CDR2L), onconeural antigens with poorly understood functions, as ER adaptors for cytoplasmic dynein-1 (dynein). We demonstrate in human cancer cells that CDR2 is recruited by the integral ER membrane protein kinectin (KTN1) and that double knockout of CDR2 and CDR2L enhances KTN1-dependent ER sheet stacking, reversal of which by exogenous CDR2 requires its dynein-binding CC1 box motif. Exogenous CDR2 expression additionally promotes CC1 box-dependent clustering of ER sheets near centrosomes. CDR2 competes with the eEF1Bβ subunit of translation elongation factor 1 for binding to KTN1, and eEF1Bβ knockdown increases endogenous CDR2 levels on ER sheets, inducing their centrosome-proximal clustering. Our study describes a novel molecular pathway that implicates dynein in ER sheet organization and may be involved in the pathogenesis of paraneoplastic cerebellar degeneration.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bing Han, Sarah M Connolly, Darrin T Schultz, Louis F L Wilson, Alican Gulsevin, Jens Meiler, Erkan Karakas, Melanie D Ohi, Anne K Kenworthy
{"title":"Evolutionarily diverse caveolins share a common structural framework built around amphipathic disks.","authors":"Bing Han, Sarah M Connolly, Darrin T Schultz, Louis F L Wilson, Alican Gulsevin, Jens Meiler, Erkan Karakas, Melanie D Ohi, Anne K Kenworthy","doi":"10.1083/jcb.202411175","DOIUrl":"10.1083/jcb.202411175","url":null,"abstract":"<p><p>Caveolins are a unique family of membrane remodeling proteins present broadly across animals (Metazoa), and in vertebrates form flask-shaped invaginations known as caveolae. While human caveolin-1 assembles into an amphipathic disk composed of 11 spirally packed protomers, the structural basis underlying caveolin function across animals remains elusive. Here, we predicted structures for 73 caveolins spanning animal diversity, as well as a newly identified choanoflagellate caveolin from Salpingoeca rosetta. This analysis revealed seven conserved structural elements and a propensity to assemble into amphipathic disks. Cryo-EM structures of caveolins from S. rosetta choanoflagellate and the purple sea urchin Strongylocentrotus purpuratus exhibit striking structural similarities to human caveolin-1, validating the structural predictions. Lastly, tracing the chromosomal evolutionary history of caveolins revealed its parahoxozoan ancestral chromosome and evolutionary branches on which caveolins translocated and expanded. These results show that caveolins possess an ancient structural framework predating Metazoa and provide a new structural paradigm to explore the molecular basis of caveolin function across diverse evolutionary lineages.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FOMO no more: NOMO and calmin extend mechanobiology to the ER.","authors":"Julie Heffler, Jan Lammerding","doi":"10.1083/jcb.202508037","DOIUrl":"10.1083/jcb.202508037","url":null,"abstract":"<p><p>Research on cellular mechanotransduction has primarily focused on the cell surface and the cytoskeleton. In this issue, Naughton et al. (https://doi.org/10.1083/jcb.202505010) identify NOMO, an endoplasmic reticulum (ER)-resident protein, as a force-bearing element with crucial roles in muscle differentiation and function. In a complementary study, Merta et al. (https://doi.org/10.1016/j.celrep.2025.115502) demonstrate that calmin physically tethers ER tubules to actin filaments at focal adhesions, modulating their function.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brigitte S Naughton, Swapnil C Devarkar, Vanessa Todorow, Sunanda Mallik, Stacey Oxendine, Sanjana Junnarkar, Yuan Ren, Julien Berro, Janine Kirstein, Yong Xiong, Christian Schlieker
{"title":"Nodal modulator (NOMO) is a force-bearing transmembrane protein required for muscle differentiation.","authors":"Brigitte S Naughton, Swapnil C Devarkar, Vanessa Todorow, Sunanda Mallik, Stacey Oxendine, Sanjana Junnarkar, Yuan Ren, Julien Berro, Janine Kirstein, Yong Xiong, Christian Schlieker","doi":"10.1083/jcb.202505010","DOIUrl":"10.1083/jcb.202505010","url":null,"abstract":"<p><p>The ER relies on membrane-shaping proteins to maintain a continuous network of sheets and tubules that host distinct biological processes. How this intricate structure of the ER membrane system is maintained under conditions of mechanical strain is incompletely understood. NOMO is an ER-resident transmembrane protein that contributes to ER morphology and is highly expressed in striated muscle. In this study, we identify a critical interface between distal Ig domains that enables NOMO to maintain ER morphology and bear mechanical forces. By incorporating two independent tension sensors in the luminal domain of NOMO, we demonstrate that NOMO assemblies experience forces in the single piconewton range, with a significant contribution from the identified interface. These newly defined features are important-if not indispensable-for myogenesis, as interface mutations affecting mechanosensitivity fail to restore the essential role of NOMO during myogenesis in a C2C12 differentiation model. Moreover, NOMO depletion impairs nematode motility, underscoring a broader functional importance in muscle physiology.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Hoon Kim, Rika Maruyama, Kwon Kim, Devin A Vertrees, Parama Paul, Kyla Britson, Nathaniel R Laughner, Deborah J Andrew
{"title":"Arc controls organ architecture through modulation of Crb and MyoII.","authors":"Ji Hoon Kim, Rika Maruyama, Kwon Kim, Devin A Vertrees, Parama Paul, Kyla Britson, Nathaniel R Laughner, Deborah J Andrew","doi":"10.1083/jcb.202409078","DOIUrl":"10.1083/jcb.202409078","url":null,"abstract":"<p><p>Precise orchestration of morphogenetic processes generates organs that are optimally positioned and the right size and shape to fit and maximize functionality. Here, we show that Arc, a large apical membrane-associated PDZ domain-containing protein, works through the apical determinant Crumbs to limit non-muscle myosin II (MyoII) activity during tissue invagination in the Drosophila salivary gland (SG). We show that loss of Arc, attenuation of Crumbs, and increased activation of MyoII leads to the simultaneous internalization of more precursor cells than normal. Consequently, mature SGs are shorter with more cells surrounding the lumen all along the tube. Correspondingly, overexpression of Arc or SG-specific knockdown of MyoII leads to longer SGs with fewer cells surrounding the lumen. Our findings support a model wherein plasma membrane (PM)-associated Crumbs stabilizes cellular junctions by limiting apical pools of activated MyoII and countering the destabilizing effects of MyoII at the PM, limiting how many cells internalize at any given time, shaping final tube geometry.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}