Morgan House,Karan Khadayat,Thomas N Trybala,Nikhil Nambiar,Elizabeth Jones,Steven M Abel,Joshua Baccile,Amit S Joshi
{"title":"Phosphatidic acid drives spatiotemporal distribution of Pex30 at ER-LD contact sites.","authors":"Morgan House,Karan Khadayat,Thomas N Trybala,Nikhil Nambiar,Elizabeth Jones,Steven M Abel,Joshua Baccile,Amit S Joshi","doi":"10.1083/jcb.202405162","DOIUrl":"https://doi.org/10.1083/jcb.202405162","url":null,"abstract":"Lipid droplets (LDs) are ubiquitous neutral lipid storage organelles that form at discrete subdomains in the ER bilayer. The assembly of these ER subdomains and the mechanism by which proteins are recruited to them is poorly understood. Here, we investigate the spatiotemporal distribution of Pex30 at the ER-LD membrane contact sites (MCSs). Pex30, an ER membrane-shaping protein, has a reticulon homology domain, a dysferlin (DysF) domain, and a Duf4196 domain. Deletion of SEI1, which codes for seipin, a highly conserved protein required for LD biogenesis, results in accumulation of Pex30 and phosphatidic acid (PA) at ER-LD contact sites. We show that PA recruits Pex30 at ER subdomains by binding to the DysF domain. The distribution of Pex30 as well as PA is also affected by phosphatidylcholine (PC) levels. We propose that PA regulates the spatiotemporal distribution of Pex30 at ER subdomains that plays a critical role in driving the formation of LDs in the ER membrane.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"18 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122186","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":"A conserved role for centriolar satellites in translation of centrosomal and ciliary proteins.","authors":"Claudia Pachinger,Jeroen Dobbelaere,Cornelia Rumpf-Kienzl,Shiviya Raina,Júlia Garcia-Baucells,Marina Sarantseva,Andrea Brauneis,Alexander Dammermann","doi":"10.1083/jcb.202408042","DOIUrl":"https://doi.org/10.1083/jcb.202408042","url":null,"abstract":"Centriolar satellites are cytoplasmic particles found in the vicinity of centrosomes and cilia whose specific functional contribution has long been unclear. Here, we identify Combover as the Drosophila ortholog of the main scaffolding component of satellites, PCM1. Like PCM1, Combover localizes to cytoplasmic foci containing centrosomal proteins and its depletion or mutation results in centrosomal and ciliary phenotypes. Strikingly, however, the concentration of satellites near centrosomes and cilia is not a conserved feature, nor do Combover foci display directed movement. Proximity interaction analysis revealed not only centrosomal and ciliary proteins, but also RNA-binding proteins and proteins involved in quality control. Further work in Drosophila and vertebrate cells found satellites to be associated with centrosomal and ciliary mRNAs, as well as evidence for protein synthesis occurring directly at satellites. Given that PCM1 depletion does not affect overall protein levels, we propose that satellites instead promote the coordinate synthesis of centrosomal and ciliary proteins, thereby facilitating the formation of protein complexes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"31 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103696","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":"Good things come in threes: Distinct C. elegans basement membranes utilize novel collagen IV trimers.","authors":"K Elkie Peebles,Andrea Page-McCaw","doi":"10.1083/jcb.202503175","DOIUrl":"https://doi.org/10.1083/jcb.202503175","url":null,"abstract":"The highly conserved basement membrane protein collagen IV is stereotypically composed of two α1 subunits and one α2 subunit. In this issue, Srinivasan et al. (https://doi.org/10.1083/jcb.202412118) show that specific C. elegans basement membranes include collagen IV trimers with other compositions, suggesting a new diversity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"48 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992091","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}
Shun-Ichi Yamashita,Ritsuko Arai,Hiroshi Hada,Benjamin Scott Padman,Michael Lazarou,David C Chan,Tomotake Kanki,Satoshi Waguri
{"title":"The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondria.","authors":"Shun-Ichi Yamashita,Ritsuko Arai,Hiroshi Hada,Benjamin Scott Padman,Michael Lazarou,David C Chan,Tomotake Kanki,Satoshi Waguri","doi":"10.1083/jcb.202408166","DOIUrl":"https://doi.org/10.1083/jcb.202408166","url":null,"abstract":"BNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) and electron tomography to reveal the tight attachment of isolation membranes (IMs) to mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures. In BNIP3/NIX-double knockout (DKO) HeLa cells, the ULK1 complex and nascent IM formed on mitochondria, but the IM did not expand. Artificial tethering of LC3B to mitochondria induced mitophagy that was equally efficient in DKO cells and WT cells. BNIP3 and NIX accumulated at the segregated mitochondrial protrusions via binding with LC3 through their LIR motifs but did not require dimer formation. Finally, the average distance between the IM and the mitochondrial surface in receptor-mediated mitophagy was significantly smaller than that in ubiquitin-mediated mitophagy. Collectively, these results indicate that BNIP3 and NIX are required for the tight attachment and expansion of the IM along the mitochondrial surface during mitophagy.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"35 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945214","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":"Atg9 is a conserved regulator of lysosome repair.","authors":"Ruoxi Wang,Eric H Baehrecke","doi":"10.1083/jcb.202504129","DOIUrl":"https://doi.org/10.1083/jcb.202504129","url":null,"abstract":"The ATG9 transmembrane protein scrambles lipids to regulate phagophore formation during autophagy. Two recent studies from Peng et al. (https://doi.org/10.1083/jcb.202411092) and De Tito et al. (https://doi.org/10.1101/2024.07.23.604321) identify ATG9 as a conserved regulator of lysosome repair in Caenorhabditis elegans and human cells, but differences in repair mechanisms exist between these taxa.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"8 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945215","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}
Fiona H Murphy,Adlin Abramian,Remco V Klaassen,Frank Koopmans,Claudia M Persoon,August B Smit,Ruud F Toonen,Matthijs Verhage
{"title":"RIM and MUNC13 membrane-binding domains are essential for neuropeptide secretion.","authors":"Fiona H Murphy,Adlin Abramian,Remco V Klaassen,Frank Koopmans,Claudia M Persoon,August B Smit,Ruud F Toonen,Matthijs Verhage","doi":"10.1083/jcb.202409196","DOIUrl":"https://doi.org/10.1083/jcb.202409196","url":null,"abstract":"Neurons release neurotransmitters from synaptic vesicles (SVs) and neuropeptides from dense-core vesicles (DCVs). The presynaptic proteins RIM and MUNC13 play key roles in both pathways. It remains unclear how DCVs are targeted to release sites and whether RIM and MUNC13 are involved in this process. Here, we show that three membrane-binding domains in RIM and MUNC13 regulate DCV exocytosis differently from SV exocytosis. Using neuropeptide secretion assays with single-vesicle resolution and peptidomics analysis of endogenous neuropeptide release in MUNC13/RIM null neurons, we demonstrate that MUNC13 is essential for DCV exocytosis. The RIM N terminus prevents MUNC13 degradation via the proteasome, and inhibiting proteasomal degradation partially rescues DCV exocytosis in RIM's absence. Unlike SV exocytosis, the PIP2-binding RIM C2B domain and MUNC13 C1-C2B polybasic face are redundant for DCV exocytosis, while the lipid-binding MUNC13 C2C domain is crucial. These results show that RIM and MUNC13 synergistically regulate DCV exocytosis through membrane interactions and reveal new mechanistic differences between SV and DCV exocytosis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"33 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932738","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}
Lieke Stockmann,Hélène Kabbech,Gert-Jan Kremers,Brent van Herk,Bas Dille,Mirjam van den Hout,Wilfred F J van IJcken,Dick H W Dekkers,Jeroen A A Demmers,Ihor Smal,Danny Huylebroeck,Sreya Basu,Niels Galjart
{"title":"KIF2A stabilizes intercellular bridge microtubules to maintain mouse embryonic stem cell cytokinesis.","authors":"Lieke Stockmann,Hélène Kabbech,Gert-Jan Kremers,Brent van Herk,Bas Dille,Mirjam van den Hout,Wilfred F J van IJcken,Dick H W Dekkers,Jeroen A A Demmers,Ihor Smal,Danny Huylebroeck,Sreya Basu,Niels Galjart","doi":"10.1083/jcb.202409157","DOIUrl":"https://doi.org/10.1083/jcb.202409157","url":null,"abstract":"Cytokinesis, the final stage of cell division, serves to physically separate daughter cells. In cultured naïve mouse embryonic stem cells, cytokinesis lasts unusually long. Here, we describe a novel function for the kinesin-13 member KIF2A in this process. In genome-engineered mouse embryonic stem cells, we find that KIF2A localizes to spindle poles during metaphase and regulates spindle length in a manner consistent with its known role as a microtubule minus-end depolymerase. In contrast, during cytokinesis we observe tight binding of KIF2A to intercellular bridge microtubules. At this stage, KIF2A maintains microtubule length and number and controls microtubule acetylation. We propose that the conversion of KIF2A from a depolymerase to a stabilizer is driven by both the inhibition of its ATPase activity, which increases lattice affinity, and a preference for compacted lattices. In turn, KIF2A might maintain the compacted microtubule state at the intercellular bridge, thereby dampening acetylation. As KIF2A depletion causes pluripotency problems and affects mRNA homeostasis, our results furthermore indicate that KIF2A-mediated microtubule stabilization prolongs cytokinesis to maintain pluripotency.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"19 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932737","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}
Guillaume D Chambaud,Vlad C Martin,Gilles R X Hickson
{"title":"Anillin links up with RhoA to break the symmetry of cytokinetic ring closure.","authors":"Guillaume D Chambaud,Vlad C Martin,Gilles R X Hickson","doi":"10.1083/jcb.202504164","DOIUrl":"https://doi.org/10.1083/jcb.202504164","url":null,"abstract":"During animal cell cytokinesis, active RhoA assembles actomyosin-based contractile rings that tend to close asymmetrically. Through imaging C. elegans zygotes, Lebedev et al. (https://doi.org/10.1083/jcb.202405182) reveal that the scaffold protein, anillin, promotes asymmetric ring closure by locally sequestering RhoA from its canonical effectors and thereby limiting actomyosin contractility.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"111 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932732","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":"Ubiquitin-SUMO tag-team wrestles acute promyelocytic leukemia.","authors":"Alfred C O Vertegaal","doi":"10.1083/jcb.202504010","DOIUrl":"https://doi.org/10.1083/jcb.202504010","url":null,"abstract":"In this issue, Jaffray and colleagues (https://doi.org/10.1083/jcb.202407133) detail the molecular machinery required to degrade the oncogene PML in response to arsenic treatment. Different posttranslational modifiers team up: ubiquitin, SUMO1, and -2/3, linked by the SUMO-targeted ubiquitin ligases TOPORS and RNF4.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"39 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932422","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}