Shuai Liu, Jie Wei, Liangyujie Zhong, Sirao Hai, Shibo Song, Chaoyi Xie, Zeyu Huang, Zihang Cheng, Jing Zhang, Anna Du, Pei Zhang, Yanling Yan, Anbing Shi
{"title":"RAB-10 cooperates with EHBP-1 to capture vesicular carriers during post-Golgi exocytic trafficking.","authors":"Shuai Liu, Jie Wei, Liangyujie Zhong, Sirao Hai, Shibo Song, Chaoyi Xie, Zeyu Huang, Zihang Cheng, Jing Zhang, Anna Du, Pei Zhang, Yanling Yan, Anbing Shi","doi":"10.1083/jcb.202410003","DOIUrl":"10.1083/jcb.202410003","url":null,"abstract":"<p><p>Post-Golgi exocytic trafficking, fundamental for secretion and cell surface component integration, remains incompletely understood at the molecular level. Here, we investigated this process using Caenorhabditis elegans and mammalian cell models, revealing a novel exocytic carrier capturing mechanism involving the small GTPase RAB-10/Rab10 and its effector EHBP-1/EHBP1. EHBP-1, localized in recycling endosomes, selectively captures RAB-10-positive lipoprotein exocytic carriers through its interaction with active RAB-10, thereby promoting the delivery of exocytic cargo to recycling endosomes. A detailed mechanistic examination demonstrated the synergy between EHBP-1's RAB-10-binding coiled-coil domain and its PI(4,5)P2-binding C2 domain in the capturing process. Of note, we identified LST-6/DENND5 as a specialized guanine nucleotide exchange factor (GEF) for RAB-10 in this particular pathway, distinct from the GEF involved in basolateral recycling. Following the RAB-10-EHBP-1-mediated capture, the exocyst complex carries out its function. Taken together, this study suggests a potential tethering mechanism for basolateral post-Golgi exocytic carriers, highlighting the coordination among membrane compartments in regulating this trafficking route.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467990","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}
Brittany MacTaggart, Junling Wang, Hsin-Yao Tang, Anna Kashina
{"title":"Arginylation of ⍺-tubulin at E77 regulates microtubule dynamics via MAP1S.","authors":"Brittany MacTaggart, Junling Wang, Hsin-Yao Tang, Anna Kashina","doi":"10.1083/jcb.202406099","DOIUrl":"10.1083/jcb.202406099","url":null,"abstract":"<p><p>Arginylation is the posttranslational addition of arginine to a protein by arginyltransferase-1 (ATE1). Previous studies have found that ATE1 targets multiple cytoskeletal proteins, and Ate1 deletion causes cytoskeletal defects, including reduced cell motility and adhesion. Some of these defects have been linked to actin arginylation, but the role of other arginylated cytoskeletal proteins has not been studied. Here, we characterize tubulin arginylation and its role in the microtubule cytoskeleton. We identify ATE1-dependent arginylation of ⍺-tubulin at E77. Ate1-/- cells and cells overexpressing non-arginylatable ⍺-tubulinE77A both show a reduced microtubule growth rate and increased microtubule stability. Additionally, they show an increase in the fraction of the stabilizing protein MAP1S associated with microtubules, suggesting that E77 arginylation directly regulates MAP1S binding. Knockdown of Map1s is sufficient to rescue microtubule growth rate and stability to wild-type levels. Together, these results demonstrate a new type of tubulin regulation by posttranslational arginylation, which modulates microtubule growth rate and stability through the microtubule-associated protein, MAP1S.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033038","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}
Haguy Wolfenson, Gregory Giannone, Martin A Schwartz
{"title":"In Memoriam: Mike Sheetz.","authors":"Haguy Wolfenson, Gregory Giannone, Martin A Schwartz","doi":"10.1083/jcb.202503048","DOIUrl":"10.1083/jcb.202503048","url":null,"abstract":"<p><p>Michael P. Sheetz made immense contributions to our understanding of motor proteins, membrane biology, cytoskeleton and mechanobiology over his ~50-year career. He started his independent career at the University of Connecticut, after which he moved to Washington University in St. Louis and then to Duke University, where he led the Department of Cell Biology for 10 years. He then moved to Columbia University, where he established a research group focused on mechanobiology, and then founded and led the Mechanobiology Institute at the National University of Singapore for 10 years. He ended his career at the University of Texas Health Center in Galveston, TX, USA. He trained a generation of leading interdisciplinary cell and mechanobiologists whose independent contributions continue to enhance his legacy.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673441","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}
Paolo Sanzà, Jan van der Beek, Derk Draper, Cecilia de Heus, Tineke Veenendaal, Corlinda Ten Brink, Ginny G Farías, Nalan Liv, Judith Klumperman
{"title":"VPS41 recruits biosynthetic LAMP-positive vesicles through interaction with Arl8b.","authors":"Paolo Sanzà, Jan van der Beek, Derk Draper, Cecilia de Heus, Tineke Veenendaal, Corlinda Ten Brink, Ginny G Farías, Nalan Liv, Judith Klumperman","doi":"10.1083/jcb.202405002","DOIUrl":"10.1083/jcb.202405002","url":null,"abstract":"<p><p>Vacuolar protein sorting 41 (VPS41), a component of the homotypic fusion and protein sorting (HOPS) complex for lysosomal fusion, is essential for the trafficking of lysosomal membrane proteins via lysosome-associated membrane protein (LAMP) carriers from the trans-Golgi network (TGN) to endo/lysosomes. However, the molecular mechanisms underlying this pathway and VPS41's role herein remain poorly understood. Here, we investigated the effects of ectopically localizing VPS41 to mitochondria on LAMP distribution. Using electron microscopy, we identified that mitochondrial-localized VPS41 recruited LAMP1- and LAMP2A-positive vesicles resembling LAMP carriers. The retention using selective hooks (RUSH) system further revealed that newly synthesized LAMPs were specifically recruited by mitochondrial VPS41, a function not shared by other HOPS subunits. Notably, we identified the small GTPase Arl8b as a critical factor for LAMP carrier trafficking. Arl8b was present on LAMP carriers and bound to the WD40 domain of VPS41, enabling their recruitment. These findings reveal a unique role of VPS41 in recruiting TGN-derived LAMP carriers and expand our understanding of VPS41-Arl8b interactions beyond endosome-lysosome fusion, providing new insights into lysosomal trafficking mechanisms.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189576","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}
Katie Linvill, Liam J Russell, Timothy E Vanderleest, Hui Miao, Yi Xie, J Todd Blankenship, Dinah Loerke
{"title":"Rectification of planar orientation angle switches behavior and replenishes contractile junctions.","authors":"Katie Linvill, Liam J Russell, Timothy E Vanderleest, Hui Miao, Yi Xie, J Todd Blankenship, Dinah Loerke","doi":"10.1083/jcb.202309069","DOIUrl":"10.1083/jcb.202309069","url":null,"abstract":"<p><p>In the early Drosophila embryo, germband elongation is driven by oriented cell intercalation through t1 transitions, where vertical (dorsal-ventral aligned) interfaces contract and then resolve into new horizontal (anterior-posterior aligned) interfaces. Here, we show that contractile events produce a continuous \"rectification\" of cell interfaces, in which interfaces systematically rotate toward more vertical orientations. As interfaces rotate, their behavior transitions from elongating to contractile regimes, indicating that the planar polarized identities of cell-cell interfaces are continuously re-interpreted in time depending on their orientation angle. Rotating interfaces acquire higher levels of Myosin II motor proteins as they become more vertical, while disruptions to the contractile molecular machinery reduce the rates of rotation. Through this angle rectification, the available pool of contractile interfaces is continuously replenished, as new interfaces acquire a contractile identity through rotation. Thus, individual cells acquire additional interfaces that are capable of undergoing t1 transitions, allowing cells to participate in multiple staggered rounds of intercalation events.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023645","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}
Diogjena Katerina Prifti, Annie Lauzier, Chantal Garand, Eva Calvo, Romain Devillers, Suparba Roy, Alexsandro Dos Santos, Laurence Descombes, Benjamin Trudel, Mathieu Laplante, François Bordeleau, Sabine Elowe
{"title":"ARHGEF17/TEM4 regulates the cell cycle through control of G1 progression.","authors":"Diogjena Katerina Prifti, Annie Lauzier, Chantal Garand, Eva Calvo, Romain Devillers, Suparba Roy, Alexsandro Dos Santos, Laurence Descombes, Benjamin Trudel, Mathieu Laplante, François Bordeleau, Sabine Elowe","doi":"10.1083/jcb.202311194","DOIUrl":"10.1083/jcb.202311194","url":null,"abstract":"<p><p>The Ras homolog (Rho) small GTPases coordinate diverse cellular functions including cell morphology, adhesion and motility, cell cycle progression, survival, and apoptosis via their role in regulating the actin cytoskeleton. The upstream regulators for many of these functions are unknown. ARHGEF17 (also known as TEM4) is a Rho family guanine nucleotide exchange factor (GEF) implicated in cell migration, cell-cell junction formation, and the mitotic checkpoint. In this study, we characterize the regulation of the cell cycle by TEM4. We demonstrate that TEM4-depleted cells exhibit multiple defects in mitotic entry and duration, spindle morphology, and spindle orientation. In addition, TEM4 insufficiency leads to excessive cortical actin polymerization and cell rounding defects. Mechanistically, we demonstrate that TEM4-depleted cells delay in G1 as a consequence of decreased expression of the proproliferative transcriptional co-activator YAP. TEM4-depleted cells that progress through to mitosis do so with decreased levels of cyclin B as a result of attenuated expression of CCNB1. Importantly, cyclin B overexpression in TEM4-depleted cells largely rescues mitotic progression and chromosome segregation defects in anaphase. Our study thus illustrates the consequences of Rho signaling imbalance on cell cycle progression and identifies TEM4 as the first GEF governing Rho GTPase-mediated regulation of G1/S.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189572","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}
Layla El Mossadeq, Laura Bellutti, Rémi Le Borgne, Julie C Canman, Lionel Pintard, Jean-Marc Verbavatz, Peter Askjaer, Julien Dumont
{"title":"An interkinetic envelope surrounds chromosomes between meiosis I and II in C. elegans oocytes.","authors":"Layla El Mossadeq, Laura Bellutti, Rémi Le Borgne, Julie C Canman, Lionel Pintard, Jean-Marc Verbavatz, Peter Askjaer, Julien Dumont","doi":"10.1083/jcb.202403125","DOIUrl":"10.1083/jcb.202403125","url":null,"abstract":"<p><p>At the end of cell division, the nuclear envelope reassembles around the decondensing chromosomes. Female meiosis culminates in two consecutive cell divisions of the oocyte, meiosis I and II, which are separated by a brief transition phase known as interkinesis. Due to the absence of chromosome decondensation and the suppression of genome replication during interkinesis, it has been widely assumed that the nuclear envelope does not reassemble between meiosis I and II. By analyzing interkinesis in C. elegans oocytes, we instead show that an atypical structure made of two lipid bilayers, which we termed the interkinetic envelope, surrounds the surface of the segregating chromosomes. The interkinetic envelope shares common features with the nuclear envelope but also exhibits specific characteristics that distinguish it, including its lack of continuity with the endoplasmic reticulum, unique protein composition, assembly mechanism, and function in chromosome segregation. These distinct attributes collectively define the interkinetic envelope as a unique and specialized structure that has been previously overlooked.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894793","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}
Alexander T Lessenger, Jan M Skotheim, Mathew P Swaffer, Jessica L Feldman
{"title":"Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output.","authors":"Alexander T Lessenger, Jan M Skotheim, Mathew P Swaffer, Jessica L Feldman","doi":"10.1083/jcb.202403154","DOIUrl":"10.1083/jcb.202403154","url":null,"abstract":"<p><p>Cell size and biosynthetic capacity generally increase with increased DNA content. Somatic polyploidy has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood. Here, we show that polyploidy in the Caenorhabditis elegans intestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with dilute mRNA. Highly expressed transcripts were more sensitive to this mRNA dilution, whereas lowly expressed genes were partially compensated-in part by loading more RNA Polymerase II on the remaining genomes. Polyploidy-deficient animals produced fewer and slower-growing offspring, consistent with reduced synthesis of highly expressed yolk proteins. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing the expression of translational machinery at the expense of specialized, cell-type-specific proteins.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800922","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":"Cytosolic companionship: Rickettsia connects with the endoplasmic reticulum.","authors":"Stacey D Gilk","doi":"10.1083/jcb.202412181","DOIUrl":"10.1083/jcb.202412181","url":null,"abstract":"<p><p>Rickettsia are bacterial pathogens known for their actin-based motility in the host cell cytoplasm. In this issue, Acevedo-Sánchez and colleagues (https://doi.org/10.1083/jcb.202406122) discover non-motile Rickettsia bacteria hijack host machinery to form stable membrane contact sites with the host endoplasmic reticulum.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390844","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":"Selective regulation of kinesin-5 function by β-tubulin carboxy-terminal tails.","authors":"Ezekiel C Thomas, Jeffrey K Moore","doi":"10.1083/jcb.202405115","DOIUrl":"10.1083/jcb.202405115","url":null,"abstract":"<p><p>The tubulin code hypothesis predicts that tubulin tails create programs for selective regulation of microtubule-binding proteins, including kinesin motors. However, the molecular mechanisms that determine selective regulation and their relevance in cells are poorly understood. We report selective regulation of budding yeast kinesin-5 motors by the β-tubulin tail. Cin8, but not Kip1, requires the β-tubulin tail for recruitment to the mitotic spindle, creating a balance of both motors in the spindle and efficient mitotic progression. We identify a negatively charged patch in the β-tubulin tail that mediates interaction with Cin8. Using in vitro reconstitution with genetically modified yeast tubulin, we demonstrate that the charged patch of β-tubulin tail increases Cin8 plus-end-directed velocity and processivity. Finally, we determine that the positively charged amino-terminal extension of Cin8 coordinates interactions with the β-tubulin tail. Our work identifies a molecular mechanism underlying selective regulation of closely related kinesin motors by tubulin tails and how this regulation promotes proper function of the mitotic spindle.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836510","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}