Traffic最新文献

{"title":"Correction to \"Eps15R and Clathrin Regulate EphB2-Mediated Cell Repulsion\".","authors":"","doi":"10.1111/tra.70012","DOIUrl":"10.1111/tra.70012","url":null,"abstract":"","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70012"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235329","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":"Golgi Localized Arl15 Regulates Cargo Transport and Cell Adhesion.","authors":"Prerna Sharma, Pooja Hoovina Venkatesh, Shalini Samal, Neha Paddillaya, Nikita Shah, B R Rajeshwari, Abhay Bhat, Deepak Kumar Nayak, Archishman Dakua, Aravind Penmatsa, Deepak Kumar Nair, Nagaraj Balasubramanian, Namrata Gundiah, Subba Rao Gangi Setty","doi":"10.1111/tra.70004","DOIUrl":"https://doi.org/10.1111/tra.70004","url":null,"abstract":"<p><p>Arf-like GTPases (Arls) regulate membrane trafficking and cytoskeletal organization. Genetic studies predicted a role for Arl15 in type-2 diabetes, insulin resistance, adiposity, and rheumatoid arthritis. Cell biological studies implicated Arl15 in regulating various cellular processes, including magnesium homeostasis and TGFβ signaling. However, the role of Arl15 in vesicular transport is poorly defined. We evaluated the function of Arl15 using techniques to quantify cargo trafficking to mechanobiology. Fluorescence microscopy of stably expressing Arl15-GFP HeLa cells showed its localization primarily to the Golgi and cell surface. The depletion of Arl15 causes the mislocalization of selective Golgi cargo, such as caveolin-2 and STX6, in the cells. Consistently, expression of GTPase-independent dominant negative mutants of Arl15 (Arl15^{V80A,A86L,E122K} and Arl15^C22Y,C23Y) results in mislocalization of caveolin-2 and STX6 from the Golgi. However, the localization of Arl15 to the Golgi is dependent on its palmitoylation and Arf1-dependent Golgi integrity. At the cellular level, Arl15 depleted cells display enhanced cell spreading and adhesion strength. Traction force microscopy experiments revealed that Arl15 depleted cells exert higher tractions and generate multiple focal adhesion points during the initial phase of cell adhesion compared to control cells. Collectively, these studies implicate a functional role for Arl15 in regulating cargo transport from the Golgi to regulate cell surface processes.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70004"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049577","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":"Re-Visiting the Intracellular Pathway of Transferrin on Board of a Mathematical Simulation.","authors":"Franco Nieto, Luis S Mayorga","doi":"10.1111/tra.70006","DOIUrl":"https://doi.org/10.1111/tra.70006","url":null,"abstract":"<p><p>Modeling and simulation are transforming all fields of biology. Tools like AlphaFold have revolutionized structural biology, while molecular dynamics simulations provide invaluable insights into the behavior of macromolecules in solution or on membranes. In contrast, we lack effective tools to represent the dynamic behavior of the endomembrane system. Static diagrams that connect organelles with arrows are used to depict transport across space and time but fail to specify the underlying mechanisms. This static representation obscures the dynamism of intracellular traffic, freezing it in an immobilized framework. The intracellular transport of transferrin, a key process for cellular iron delivery, is among the best-characterized trafficking pathways. In this commentary, we revisit this process using a mathematical simulation of the endomembrane system. Our model reproduces many experimental observations and highlights the strong contrast between dynamic simulations and static illustrations. This commentary underscores the urgent need for a consensus-based minimal functional working model for the endomembrane system and emphasizes the importance of generating more quantitative experimental data-including precise measurements of organelle size, volume and transport kinetics-practices that were more common among cell biologists in past decades.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70006"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050075","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":"Salmonella Typhimurium Manipulates Syntaxin 7 to Navigate Endo-Lysosomal Trafficking in Host Cells.","authors":"Rhea Vij, Ritika Chatterjee, Abhilash Vijay Nair, Anmol Singh, Dipasree Hajra, Subba Rao Gangi Setty, Dipshikha Chakravortty","doi":"10.1111/tra.70010","DOIUrl":"10.1111/tra.70010","url":null,"abstract":"<p><p>Intracellular pathogens rely on manipulating host endocytic pathways to ensure survival. Legionella and Chlamydia exploit host SNARE proteins, with Legionella cleaving syntaxin 17 (STX17) and Chlamydia interacting with VAMP8 and VAMP7. Similarly, Salmonella targets the host's endosomal fusion machinery, using SPI effectors like SipC and SipA to interact with syntaxin 6 (STX6) and syntaxin 8 (STX8), respectively, maintaining its vacuolar niche. Recent evidence highlights syntaxin 7 (STX7), a Qa-SNARE involved in endo-lysosomal fusion, as a potential Salmonella target. BioID screening revealed STX7 interactions with SPI-2 effectors SifA and SopD2, suggesting a critical role in Salmonella pathogenesis. We investigated the role of STX7 in Salmonella-containing vacuole (SCV) biogenesis and pathogenesis in macrophages and epithelial cells. Our findings indicate that STX7 levels and localization differ between these cell types during infection, reflecting the distinct survival strategies of Salmonella. Live cell imaging showed that STX7 is recruited to SCVs at different infection stages, with significantly altered distribution in HeLa cells at the late stage of infection. STX7 knockdown resulted in reduced bacterial survival, which was rescued upon overexpression of STX7 in both HeLa and RAW264.7 cells, suggesting Salmonella hijacks STX7 to evade lysosomal fusion and secure nutrients for intracellular replication. These results underscore the essential role of STX7 in maintaining SCVs and facilitating Salmonella survival. Further, the temporal expression of STX7 adaptor/binding partners in macrophages showed dynamic interactions with STX7 facilitating Salmonella infection and survival in host cells. Together, our study highlights STX7 as a critical host factor exploited by Salmonella, providing insights into the molecular mechanisms underlying its pathogenesis in macrophages and epithelial cells. These findings may inform strategies for targeting host-pathogen interactions to combat Salmonella infections.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70010"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183186","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":"Identification of Rab GTPase-Activating Proteins Required for Tubular Endosome Formation.","authors":"Shumpei Nakashima, Mitsunori Fukuda","doi":"10.1111/tra.70007","DOIUrl":"https://doi.org/10.1111/tra.70007","url":null,"abstract":"<p><p>In certain kinds of cells, clathrin-independently endocytosed cargo proteins are recycled back to the plasma membrane via specialized tubular-shaped endosomes, so-called tubular endosomes. Several regulators, including Rab small GTPases, have previously been reported to control tubular endosome structures, and one of the regulators, Rab22A, controls cargo sorting and tubule elongation. Since Rab activity is generally controlled by a guanine nucleotide exchange factor (GEF) and a GTPase-activating protein (GAP), these upstream regulators would also be involved in tubular endosome formation. However, although we have previously reported that Vps9d1 is a Rab22A-GEF that controls tubular endosome formation, there have been no reports of Rab-GAPs that are required for tubular endosome formation. Here, we demonstrated by comprehensive screening of TBC/Rab-GAPs that four Rab-GAPs, TBC1D10B, TBC1D18, TBC1D22B and EVI5, are involved in tubular endosome formation in HeLa cells in a GAP-activity-dependent manner. Knockdown or overexpression of each of these Rab-GAPs resulted in the same phenotype, that is, reduced tubular endosome structures. Since one of these four Rab-GAPs, TBC1D10B, was able to reduce the amount of active Rab22A and the size of Rab22A-positive early endosomes, it is the most probable candidate for a Rab22A-GAP. Our findings suggest that a proper GTPase cycle is important for the control of tubular endosome formation.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70007"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015672","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":"Acute GARP Depletion Disrupts Vesicle Transport, Leading to Severe Defects in Sorting, Secretion and O-Glycosylation.","authors":"Amrita Khakurel, Irina Pokrovskaya, Walter S Aragon-Ramirez, Vladimir V Lupashin","doi":"10.1111/tra.70003","DOIUrl":"10.1111/tra.70003","url":null,"abstract":"<p><p>The GARP complex is an evolutionarily conserved protein complex proposed to tether endosome-derived vesicles at the trans-Golgi network. While complete depletion of the GARP leads to severe trafficking and glycosylation defects, the primary defects linked to GARP dysfunction remain unclear. In this study, we utilized the mAID degron strategy to achieve rapid degradation of VPS54 in human cells, acutely disrupting GARP function. This resulted in the partial mislocalization and degradation of a subset of Golgi-resident proteins, including TGN46, ATP7A, TMEM87A, CPD, C1GALT1 and GS15. Enzyme recycling defects led to O-glycosylation abnormalities. Additionally, while fibronectin and cathepsin D secretion were altered, mannose-6-phosphate receptors were largely unaffected. Partial displacement of COPI, AP1 and GGA coats caused a significant accumulation of vesicle-like structures and large vacuoles. Electron microscopy detection of GARP-dependent vesicles and identifying specific cargo proteins provide direct experimental evidence of GARP's role as a vesicular tether. We conclude that the primary defects of GARP dysfunction involve vesicular coat mislocalization, accumulation of GARP-dependent vesicles, degradation and mislocalization of specific Golgi proteins and O-glycosylation defects.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 1-3","pages":"e70003"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658677","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":"Disease-Associated Factors at the Endoplasmic Reticulum-Golgi Interface.","authors":"Miharu Maeda, Masashi Arakawa, Kota Saito","doi":"10.1111/tra.70001","DOIUrl":"10.1111/tra.70001","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER)-Golgi interface is essential for directing the transport of proteins synthesized in the ER to the Golgi apparatus via the ER-Golgi intermediate compartment, as well as for recycling proteins back to the ER. This transport is facilitated by various components, including COPI and COPII coat protein complexes and the transport protein particle complex. Recently, the ER-Golgi transport pathway has gained attention due to emerging evidence of nonvesicular transport mechanisms and the regulation of trafficking through liquid-liquid phase separation. Numerous diseases have been linked to mutations in proteins localized at the ER-Golgi interface, highlighting the need for comprehensive analysis of these conditions. This review examines the disease phenotypes associated with dysfunctional ER-Golgi transport factors and explores their cellular effects, providing insights into potential therapeutic strategies.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 1-3","pages":"e70001"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568248","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":"Adaptor-Mediated Trafficking of Tank Binding Kinase 1 During Diverse Cellular Processes.","authors":"Swagatika Paul, Sahitya Ranjan Biswas, Julia P Milner, Porter L Tomsick, Alicia M Pickrell","doi":"10.1111/tra.70000","DOIUrl":"10.1111/tra.70000","url":null,"abstract":"<p><p>The serine/threonine kinase, Tank Binding Kinase 1 (TBK1), drives distinct cellular processes like innate immune signaling, selective autophagy, and mitosis. It is suggested that the translocation and activation of TBK1 at different subcellular locations within the cell, downstream of diverse stimuli, are driven by TBK1 adaptor proteins forming a complex directly or indirectly with TBK1. Various TBK1 adaptors and associated proteins like NAP1, TANK, SINTBAD, p62, optineurin (OPTN), TAX1BP1, STING, and NDP52 have been identified in facilitating TBK1 activation and recruitment with varying overlapping redundancy. This review focuses on what is known about these proteins, their interactions with TBK1, and the functional consequences of these associations. We shed light on underexplored areas of research on these TBK1 binding partners while emphasizing how future research is required to understand the function and flexibility of TBK1 signaling and crosstalk or regulation between different biological processes.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 1-3","pages":"e70000"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568232","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":"Computational Modeling Reveals a Catch-and-Guide Interaction Between Kinesin-1 and Tubulin C-Terminal Tails.","authors":"Trini Nguyen, Steven P Gross, Christopher E Miles","doi":"10.1111/tra.70002","DOIUrl":"10.1111/tra.70002","url":null,"abstract":"<p><p>The delivery of intracellular cargoes by kinesins is modulated at scales ranging from the geometry of the microtubule networks down to interactions with individual tubulins and their code. The complexity of the tubulin code and the difficulty in directly observing motor-tubulin interactions have hindered progress in pinpointing the precise mechanisms by which kinesin's function is modulated. As one such example, past experiments show that cleaving tubulin C-terminal tails (CTTs) lowers kinesin-1's processivity and velocity on microtubules, but how these CTTs intertwine with kinesin's processive cycle remains unclear. In this work, we formulate and interrogate several plausible mechanisms by which CTTs contribute to and modulate kinesin motion. Computational modeling bridges the gap between effective transport observations (processivity, velocities) and microscopic mechanisms. Ultimately, we find that a guiding mechanism can best explain the observed differences in processivity and velocity. Altogether, our work adds a new understanding of how the CTTs and their modulation via the tubulin code may steer intracellular traffic in both health and disease.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 1-3","pages":"e70002"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617257","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":"PcloC-Mediated Phase Separation in Short-Distance Vesicle Transport.","authors":"Huyong Yan, Yixuan Deng","doi":"10.1111/tra.12959","DOIUrl":"10.1111/tra.12959","url":null,"abstract":"<p><p>Phase separation is increasingly recognized as a paradigm to elucidate the self-assembly and organization of membrane-less bodies within the cell, which involves the segregation of a multi-component system into distinct phases with varying compositions and structures. The latest study has found that protein aggregates formed through phase separation can effectively realize short-distance transport of vesicles. PcloC responds to calcium through C2A domain-mediated calcium sensing, thereby extracting synaptic vesicles from the reserve pool where synaptic proteins aggregate into the surface of the active zone protein condensate. Therefore, PcloC-mediated phase separation may provide a new perspective to understanding short-distance directional transport within cells.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 11-12","pages":"e12959"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256830","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}