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Investigating Translocation Mechanisms of TDP-43 Into the Endoplasmic Reticulum Using Budding Yeast Models. 利用芽殖酵母模型研究TDP-43在内质网中的易位机制。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-09-01 DOI: 10.1111/tra.70054
Miku Saito, Hana Tsuzuki, Akira Hosomi
{"title":"Investigating Translocation Mechanisms of TDP-43 Into the Endoplasmic Reticulum Using Budding Yeast Models.","authors":"Miku Saito, Hana Tsuzuki, Akira Hosomi","doi":"10.1111/tra.70054","DOIUrl":"10.1111/tra.70054","url":null,"abstract":"<p><p>Signal peptides direct secretory and membrane proteins to the endoplasmic reticulum (ER), but proteins lacking classical signal peptides can occasionally engage the ER translocation machinery. TDP-43 is a nuclear RNA-binding protein implicated in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 pathology has been linked to extracellular TDP-43 species, association with the ER luminal oxidoreductase PDI, and ER stress-related phenotypes, yet whether TDP-43 fragments can directly access the ER lumen remains unclear. Here, we used budding yeast to examine signal peptide-independent ER entry of TDP-43. C-terminal fragments of TDP-43 acquired N-glycans in ste24Δ cells, whereas full-length TDP-43 showed little detectable ER entry. Endo H digestion confirmed N-glycosylation of the fragments, and a protease protection assay supported ER luminal localization of TDP-43(Δ2-89). ER entry was reduced by sec61-41 and sec66Δ, indicating engagement of a Sec61/Sec66-dependent translocation pathway. Deletion analyses identified opposing sequence elements: residues 320-343 facilitated ER entry, whereas an N-terminal region upstream of the nuclear localization signal suppressed it. TDP-43(Δ2-89) also accessed the secretory pathway, and selected disease-associated variants caused Ire1-dependent growth vulnerability without increasing detectable ER translocation. These findings reveal a Ste24-suppressed route for noncanonical ER entry of TDP-43 fragments.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 3","pages":"e70054"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921111","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}
引用次数: 0
From Pits to Plaques: Electron Microscopy Reveals Clathrin Structural Plasticity in Trafficking, Sorting and Adhesion. 从凹坑到斑块:电子显微镜揭示网格蛋白在运输、分选和粘附中的结构可塑性。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-09-01 DOI: 10.1111/tra.70053
Marion Benoist, Stéphane Vassilopoulos
{"title":"From Pits to Plaques: Electron Microscopy Reveals Clathrin Structural Plasticity in Trafficking, Sorting and Adhesion.","authors":"Marion Benoist, Stéphane Vassilopoulos","doi":"10.1111/tra.70053","DOIUrl":"10.1111/tra.70053","url":null,"abstract":"<p><p>Clathrin-mediated trafficking has classically been described through the formation of curved clathrin-coated pits and vesicles. However, growing evidence indicates that clathrin assembles into a diverse array of membrane-associated architectures whose geometry, dynamics, and function vary across cellular compartments and physiological contexts. These include canonical coated pits at the plasma membrane and trans-Golgi network, extended flat lattices and plaques at the cell surface, clathrin coats associated with endosomal sorting domains, and tubular clathrin assemblies associated with three-dimensional migration. Here, we synthesize recent work, including cell-type-specific, mechanobiological, and ultrastructural studies, to propose clathrin structural plasticity as a core organizing principle of intracellular trafficking. We discuss how adaptor identity, membrane lipid composition, cytoskeletal coupling, and mechanical constraints collectively shape clathrin architectures, enabling a single coat system to support vesicular transport, cargo sorting, signaling, and adhesion.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 3","pages":"e70053"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841391","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}
引用次数: 0
Mechanism of Autophagic Extracellular Vesicles Revealed. 揭示自噬细胞外囊泡的机制。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-09-01 DOI: 10.1111/tra.70045
Constantinos Demetriades, Thierry Galli
{"title":"Mechanism of Autophagic Extracellular Vesicles Revealed.","authors":"Constantinos Demetriades, Thierry Galli","doi":"10.1111/tra.70045","DOIUrl":"10.1111/tra.70045","url":null,"abstract":"<p><p>Recent work by Mao and colleagues identifies a distinct class of small extracellular vesicles, termed autophagic extracellular vesicles (AEVs), generated from amphisomes upon autophagy induction. In this commentary, we discuss how this study provides important mechanistic insight into the coupling between autophagy and secretion. AEVs are molecularly and functionally distinct from canonical exosomes, being enriched in autophagy-related components such as LC3 and p62, and dependent on core ATG machinery for their biogenesis. Notably, their secretion is enhanced by autophagy induction and contributes to intercellular communication, particularly in the context of viral infection. These findings position amphisomes as critical sorting hubs that direct cargo toward either degradation or secretion, thereby integrating autophagic and endolysosomal pathways. We further highlight how these results intersect with prior evidence implicating SNARE-dependent mechanisms, including VAMP7 and stress-responsive regulators such as GRASP55, in unconventional secretion. Finally, we discuss key unresolved questions, particularly the mechanisms underlying the generation of small intraluminal vesicles within amphisomes and the role of ESCRT machinery in this process. Overall, the identification of AEVs adds a new layer of complexity to extracellular vesicle biology and opens new avenues for understanding how autophagy contributes to intercellular signaling in health and disease.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 3","pages":"e70045"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707849","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}
引用次数: 0
Interview With Barbara Pearse and the Clathrin Family Tree. 采访芭芭拉·皮尔斯和网格蛋白家谱。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-09-01 DOI: 10.1111/tra.70048
Frances M Brodsky, Margaret S Robinson
{"title":"Interview With Barbara Pearse and the Clathrin Family Tree.","authors":"Frances M Brodsky, Margaret S Robinson","doi":"10.1111/tra.70048","DOIUrl":"10.1111/tra.70048","url":null,"abstract":"<p><p>The clathrin family tree. Timeline of research on clathrin leading to and generated by Barbara Pearse's discovery, with milestones mapped onto the clathrin triskelion.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 3","pages":"e70048"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831920","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}
引用次数: 0
"S-Tau-Lled" Lysosomes Disrupt Autophagic Processes in Neurodegeneration. “s - tau - lll”溶酶体破坏神经退行性疾病的自噬过程。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-09-01 DOI: 10.1111/tra.70051
Anaïs Bécot, Mehdi Kabani
{"title":"\"S-Tau-Lled\" Lysosomes Disrupt Autophagic Processes in Neurodegeneration.","authors":"Anaïs Bécot, Mehdi Kabani","doi":"10.1111/tra.70051","DOIUrl":"10.1111/tra.70051","url":null,"abstract":"<p><p>Tauopathies are a class of neurodegenerative diseases characterized by the accumulation of hyperphosphorylated, misfolded and aggregated Tau proteins and by dysfunctions in the autophagy-lysosome system. Whether the latter are a cause or a consequence of the former is unclear. The answer may come from a recent study by Mirfakhar et al. Using human iPSC-derived neurons harboring the MAPT p.R406W mutation in Tau, they were able to show that pathogenic Tau is able to broadly impair lysosomal function ahead of Tau accumulation. They also show that the degradative function of lysosomes, but not their motility, can be restored through pharmacological activation of autophagy, leading to reduced Tau levels. This work opens new therapeutic opportunities to eliminate early-on pathological misfolded Tau proteins before they can engage in a vicious cycle of aggregation, amplification and propagation.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 3","pages":"e70051"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901154","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}
引用次数: 0
Clathrin-Mediated Endocytosis in Plants: Historical to Modern Advances. 植物中网格蛋白介导的内吞作用:从历史到现代进展。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-06-01 DOI: 10.1111/tra.70037
Timber Mattson, Sebastian Bednarek, Alex Johnson
{"title":"Clathrin-Mediated Endocytosis in Plants: Historical to Modern Advances.","authors":"Timber Mattson, Sebastian Bednarek, Alex Johnson","doi":"10.1111/tra.70037","DOIUrl":"10.1111/tra.70037","url":null,"abstract":"<p><p>Clathrin-mediated endocytosis (CME) is vital to plant physiology; however, the molecular details of how it functions in these complex multicellular eukaryotes remain to be defined relative to model yeast and animal systems. In this review, we explore potential reasons for this including a discussion of the debate of the existence of CME in plants, and the development of tools which have recently advanced our understanding of plant CME, including visualisation of live CME events in intact plants, and ultrastructural and proteomic analysis of plant clathrin-coated vesicles. In addition, we present an updated schematic of the temporal and spatially distinct stages of plant CME that attempts to consolidate our current understanding and to serve as a working model for further study of plant CME. Plants occupy a distinct branch of the evolutionary tree of life relative to yeast and animal systems with their own cellular constraints (e.g., extremely high intracellular turgor pressure conditions). Thus, while the core CME machinery that was predicted to have already been present in the Last Eukaryotic Common Ancestor is conserved in plants, it has needed to evolve to overcome these plant cellular constraints. Thus, in this review, we wish to highlight plants as important model organisms for understanding the overall principles governing CME and how it can adapt in mechanically and biochemically distinct ways.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 2","pages":"e70037"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943001","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}
引用次数: 0
A Toolbox for Quantifying Nuclear and Nucleolar Protein Accumulation Using NLS and NoLS Fusion Reporters. 使用NLS和NoLS融合报告器定量核和核仁蛋白积累的工具箱。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-06-01 DOI: 10.1111/tra.70036
Eugene A Arifulin, Yana R Musinova, Ulyana V Matveeva, Eugene V Sheval
{"title":"A Toolbox for Quantifying Nuclear and Nucleolar Protein Accumulation Using NLS and NoLS Fusion Reporters.","authors":"Eugene A Arifulin, Yana R Musinova, Ulyana V Matveeva, Eugene V Sheval","doi":"10.1111/tra.70036","DOIUrl":"10.1111/tra.70036","url":null,"abstract":"<p><p>Fluorescent proteins that are fused to nuclear localization signals (NLSs) or nucleolar localization signals (NoLSs) are commonly used to investigate the accumulation of proteins within the nucleus and nucleolus. These reporters allow for the in vivo evaluation of signal sequence function, independent of the surrounding protein context. Here, we present a standardized protocol for measuring nuclear and nucleolar accumulation using NLS- and NoLS-fusion reporters. The workflow integrates plasmid construction, transfection, expression control, imaging and computational analysis to minimize artifacts and enhance reproducibility. This framework provides a robust basis for the reliable quantification of NLS- and NoLS-mediated localization and allows for the comparison of nuclear transport mechanisms across studies.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 2","pages":"e70036"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782099","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}
引用次数: 0
Mechanistic Insight Into Clathrin-Mediated Endocytosis in Plants. 植物网格蛋白介导的胞吞作用机制研究。
IF 2.5 3区 生物学
Traffic Pub Date : 2026-06-01 DOI: 10.1111/tra.70040
Tingyu Zhu, Ive De Smet, Daniël Van Damme
{"title":"Mechanistic Insight Into Clathrin-Mediated Endocytosis in Plants.","authors":"Tingyu Zhu, Ive De Smet, Daniël Van Damme","doi":"10.1111/tra.70040","DOIUrl":"10.1111/tra.70040","url":null,"abstract":"<p><p>Clathrin-mediated endocytosis (CME) is an essential and conserved process in all eukaryotes. Plants, however, have evolutionarily retained remarkable endocytic machinery that distinguishes them from yeast and animals. In plants, CME execution involves the cooperative action of the heterotetrameric Adaptor protein 2 complex (AP-2) and the hetero-octameric TPLATE complex (TPC). Plants furthermore rely on the concerted action of two types of dynamin-related proteins during the final stages of clathrin-coated vesicle formation and do not use the actin cytoskeleton to generate the force to initiate membrane bending. Plants also rely more on phosphorylation and ubiquitination, rather than on canonical linear motifs, to integrate cargo sorting with endocytic dynamics. This review covers the entire process of CME in plants. It emphasizes recent advances in our mechanistic understanding of the process and highlights similarities and differences between plants and other model systems.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 2","pages":"e70040"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212556","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}
引用次数: 0
KIF5B and Dynein-Dependent Golgi Organization: Role in Adhesion-Dependent Microtubule Acetylation. KIF5B和动力蛋白依赖性高尔基组织:在粘附依赖性微管乙酰化中的作用。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-06-01 DOI: 10.1111/tra.70033
Antara Chakraborty, Sharvari M Pitke, Rajeshwari Br, Anwesha Dasgupta, Natasha Buwa, Rajalaxmi Behera, Madhavan Jayakrishnan, Nagaraj Balasubramanian
{"title":"KIF5B and Dynein-Dependent Golgi Organization: Role in Adhesion-Dependent Microtubule Acetylation.","authors":"Antara Chakraborty, Sharvari M Pitke, Rajeshwari Br, Anwesha Dasgupta, Natasha Buwa, Rajalaxmi Behera, Madhavan Jayakrishnan, Nagaraj Balasubramanian","doi":"10.1111/tra.70033","DOIUrl":"10.1111/tra.70033","url":null,"abstract":"<p><p>Cell-matrix adhesion regulates Golgi organization along microtubules (MTs), though how it couples with motor-driven Golgi positioning and function remains unclear. Our earlier work showed that loss of adhesion preferentially reduces Arf1 activation at the trans-Golgi (relative to cis-Golgi), possibly affecting dynein recruitment and could cause greater trans-Golgi disorganization along MTs. We now show that this differential Golgi disorganization leads to decreased MT acetylation, which recovers upon re-adhesion. Active Arf1 overexpression in non-adherent fibroblasts prevents Golgi disorganization and sustains MT acetylation, as also observed in T24 cancer cells. Using active-Arf1 pulldown, PLA and Co-immunoprecipitation studies, we further reveal that active Arf1 recruits KIF5B to the Golgi alongside dynein. siRNA-mediated knockdown (KD) of KIF5B or dynein disperses the Golgi into ministacks. In KD cells, loss of the juxtanuclear Golgi ribbon disrupts MT organization, which is also affected by altered MTOC positioning upon dynein KD. Notably, dispersed Golgi ministacks in single motor KDs maintain MT acetylation levels in both adherent and non-adherent cells. Dual KIF5B-dynein KD keeps the Golgi juxtanuclear but uniquely compact, supporting MT acetylation. This impairs Golgi-dependent trafficking and affects cell spreading, polarity and migration. Together, these reveal the Arf1-KIF5B-dynein crosstalk as a key regulator of adhesion-dependent Golgi organization and function.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 2","pages":"e70033"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499842","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}
引用次数: 0
Unraveling the Dynamics of Oxytocin in Hypothalamic Neurons. 揭示下丘脑神经元中催产素的动态。
IF 2.8 3区 生物学
Traffic Pub Date : 2026-06-01 DOI: 10.1111/tra.70034
Beatriz Aznar-Escolano, Vera Egorova, José Villanueva, Luis Miguel Gutiérrez, Virginia González-Vélez, Amparo Gil, Sandra Jurado
{"title":"Unraveling the Dynamics of Oxytocin in Hypothalamic Neurons.","authors":"Beatriz Aznar-Escolano, Vera Egorova, José Villanueva, Luis Miguel Gutiérrez, Virginia González-Vélez, Amparo Gil, Sandra Jurado","doi":"10.1111/tra.70034","DOIUrl":"10.1111/tra.70034","url":null,"abstract":"<p><p>Oxytocin plays a critical role in social behavior and maternal physiology, yet the intracellular dynamics of oxytocin-containing vesicles in neurons remain poorly characterized. Here, we combine experimental data from live cell imaging of oxytocin-containing compartments with computational analysis to investigate their mobility within hypothalamic neurons. Using machine learning-based trajectory classification, we reveal that the majority of oxytocin compartments exhibit subdiffusive motion, suggesting constraints imposed by the complex intracellular environment. This behavior likely reflects interactions with cytoskeletal structures, vesicle maturation states, or localized functional demands. Our findings provide new insights into the intracellular trafficking of neuropeptides and highlight the utility of data-driven approaches for uncovering mechanisms of neurophysiological relevance.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"27 2","pages":"e70034"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628628","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}
引用次数: 0
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