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The rapidly expanding role of LC3-interacting regions in autophagy. lc3相互作用区域在自噬中的作用迅速扩大。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-24 DOI: 10.1083/jcb.202504076
Brian J North,Dorotea Fracchiolla,Michael J Ragusa,Sascha Martens,Christopher J Shoemaker
{"title":"The rapidly expanding role of LC3-interacting regions in autophagy.","authors":"Brian J North,Dorotea Fracchiolla,Michael J Ragusa,Sascha Martens,Christopher J Shoemaker","doi":"10.1083/jcb.202504076","DOIUrl":"https://doi.org/10.1083/jcb.202504076","url":null,"abstract":"LC3-interacting regions (LIRs), or Atg8-interacting motifs (AIMs), are short linear motifs found in unstructured loops or intrinsically disordered regions of many autophagy-related proteins. LIRs were initially identified for their role in binding to Atg8 family proteins on autophagosomal membranes. However, emerging evidence suggests that LIRs and their surrounding residues mediate interactions with a wide array of proteins beyond Atg8s. This broadens the biological significance of LIRs in autophagy, rendering them an organizing principle of the autophagy machinery. In this perspective, we explore recent advances highlighting the multifunctional roles of LIRs, including their capacity to mediate binding with diverse factors. We discuss insights into the mechanisms underlying LIR-mediated interactions and propose an updated model to explain Atg8 diversification in higher eukaryotes. We conclude by addressing key challenges and outlining future directions for understanding LIR biology and its broader implications for cellular homeostasis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"700 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693223","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}
引用次数: 0
Ubiquitin chain variability directs substrates of the Tul1 ubiquitin ligase complex to different degradation pathways. 泛素链可变性指导底物的Tul1泛素连接酶复合物到不同的降解途径。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-22 DOI: 10.1083/jcb.202312133
Devon D Dennison,Ryan D Baldridge
{"title":"Ubiquitin chain variability directs substrates of the Tul1 ubiquitin ligase complex to different degradation pathways.","authors":"Devon D Dennison,Ryan D Baldridge","doi":"10.1083/jcb.202312133","DOIUrl":"https://doi.org/10.1083/jcb.202312133","url":null,"abstract":"Cellular protein quality control consists of multiple, networked systems that survey and maintain a healthy eukaryotic proteome. In Saccharomyces cerevisiae, the transmembrane ubiquitin ligase 1 (Tul1) complex is an integral membrane protein quality control system that functions within the Golgi-endosomal system. Golgi-localized Tul1 complexes target proteins for degradation by either the cytosolic proteasome or the vacuole. To understand how the complex directs substrates for degradation, we developed high-throughput functional assays for deep mutational scanning analysis of the Tul1 ubiquitin ligase. We identified mutations that disrupted Tul1 interactions with the complex or altered complex specificity by disrupting substrate polyubiquitination. This work demonstrates that Tul1 plays an important role in directing substrate degradation by influencing polyubiquitin chain length and provides tools for future study of the complex.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"98 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684242","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}
引用次数: 0
B cell mechanotransduction via ATAT1 coordinates actin and lysosomal dynamics at the immune synapse. 通过ATAT1的B细胞机械转导协调免疫突触的肌动蛋白和溶酶体动力学。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-21 DOI: 10.1083/jcb.202407181
Pablo Aceitón,Isidora Riobó,Felipe Del Valle Batalla,Jheimmy Diaz-Muñoz,Romina Ulloa,Fernanda Cabrera Reyes,Teemly Contreras,Sara Hernández-Pérez,Pieta K Mattila,María Isabel Yuseff
{"title":"B cell mechanotransduction via ATAT1 coordinates actin and lysosomal dynamics at the immune synapse.","authors":"Pablo Aceitón,Isidora Riobó,Felipe Del Valle Batalla,Jheimmy Diaz-Muñoz,Romina Ulloa,Fernanda Cabrera Reyes,Teemly Contreras,Sara Hernández-Pérez,Pieta K Mattila,María Isabel Yuseff","doi":"10.1083/jcb.202407181","DOIUrl":"https://doi.org/10.1083/jcb.202407181","url":null,"abstract":"B cells extract immobilized antigens via immune synapse formation, a process influenced by the physical properties of the antigen-presenting surface. However, the mechanisms linking mechanotransduction to antigen extraction and processing remain poorly understood. Here, we show that B cells activated on stiff substrates initiate mechanotransduction responses that drive the translocation of the microtubule acetylase ATAT1 from the nucleus to the cytoplasm, leading to increased α-tubulin acetylation. This modification releases GEF-H1 at the immune synapse, where it promotes the formation of actin foci essential for antigen extraction. Acetylated microtubules also enable B cells to stabilize and position lysosomes at the synapse center, thereby coupling actin-dependent extraction to antigen processing and presentation. Accordingly, ATAT1-silenced B cells fail to concentrate actin foci and lysosomes at the synaptic interface, resulting in impaired antigen extraction and presentation to T cells. Overall, these findings underscore how BCR-dependent mechanotransduction induces microtubule modifications to orchestrate lysosome positioning and actin remodeling at the immune synapse.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"31 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669399","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}
引用次数: 0
Protein Kinase C promotes peroxisome biogenesis and peroxisome-endoplasmic reticulum interaction. 蛋白激酶C促进过氧化物酶体的生物发生和过氧化物酶体与内质网的相互作用。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-21 DOI: 10.1083/jcb.202505040
Anya Borisyuk,Charlotte Howman,Sundararaghavan Pattabiraman,Daniel Kaganovich,Triana Amen
{"title":"Protein Kinase C promotes peroxisome biogenesis and peroxisome-endoplasmic reticulum interaction.","authors":"Anya Borisyuk,Charlotte Howman,Sundararaghavan Pattabiraman,Daniel Kaganovich,Triana Amen","doi":"10.1083/jcb.202505040","DOIUrl":"https://doi.org/10.1083/jcb.202505040","url":null,"abstract":"Peroxisomes carry out a diverse set of metabolic functions, including oxidation of very long-chain fatty acids, degradation of D-amino acids and hydrogen peroxide, and bile acid production. Many of these functions are upregulated on demand; therefore, cells control peroxisome abundance, and by extension peroxisome function, in response to environmental and developmental cues. The mechanisms upregulating peroxisomes in mammalian cells have remained unclear. Here, we identify a signaling regulatory network that coordinates cellular demand for peroxisomes and peroxisome abundance by regulating peroxisome proliferation and interaction with ER. We show that PKC promotes peroxisome PEX11b-dependent formation. PKC activation leads to an increase in peroxisome-ER contact site formation through inactivation of GSK3β. We show that removal of VAPA and VAPB impairs peroxisome biogenesis and PKC regulation. During neuronal differentiation, active PKC leads to a significant increase in peroxisome formation. We propose that peroxisomal regulation by transient PKC activation enables fine-tuned responses to the need for peroxisomal activity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"20 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669406","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}
引用次数: 0
Driven to cannibalism: A hormonal trigger for phagocytosis. 同类相食:吞噬作用的荷尔蒙触发。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-17 DOI: 10.1083/jcb.202506198
Amanda M Powell,Elizabeth T Ables
{"title":"Driven to cannibalism: A hormonal trigger for phagocytosis.","authors":"Amanda M Powell,Elizabeth T Ables","doi":"10.1083/jcb.202506198","DOIUrl":"https://doi.org/10.1083/jcb.202506198","url":null,"abstract":"In this issue, Ghosh et al. (https://doi.org/10.1083/jcb.202411073) reveal that a hormonal cue induces ovarian stretch follicle cells to cannibalize adjacent nurse cells-a process necessary to remodel egg chambers into viable eggs.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"13 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646016","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}
引用次数: 0
A biotin-HaloTag ligand enables efficient affinity capture of protein variants from live cells. 生物素-卤素标签配体能够有效地从活细胞中捕获蛋白质变体。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-16 DOI: 10.1083/jcb.202410025
Anoop Kumar Yadav,Abhijeet S Jadhav,Pawel M Szczepanik,Paolo Fagherazzi,Ivo Kabelka,Robert Vácha,Jakub Svenda,Hana Polasek-Sedlackova
{"title":"A biotin-HaloTag ligand enables efficient affinity capture of protein variants from live cells.","authors":"Anoop Kumar Yadav,Abhijeet S Jadhav,Pawel M Szczepanik,Paolo Fagherazzi,Ivo Kabelka,Robert Vácha,Jakub Svenda,Hana Polasek-Sedlackova","doi":"10.1083/jcb.202410025","DOIUrl":"https://doi.org/10.1083/jcb.202410025","url":null,"abstract":"HaloTag technology represents a versatile tool for studying proteins. Fluorescent HaloTag ligands employed in sequential labeling led to the discovery of distinct protein variants for histones, cohesins, and MCM complexes. However, an efficient biochemical approach to separate these distinct protein variants to study their biological functions is missing. Principally, being a gap in technology, the HaloTag toolbox lacks affinity ligands displaying good cell permeability and efficient affinity capture. Here, we describe the design, synthesis, and validation of a new cell-permeable biotin-HaloTag ligand, which allows rapid labeling of Halo-tagged proteins in live cells and their efficient separation using streptavidin pull-down. We provide a proof-of-concept application of how to use the herein-developed affinity ligand in sequential labeling to biochemically separate protein variants and study their biological properties. This approach enables to address fundamental questions concerning essential cellular processes, including genome duplication and chromatin maintenance.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"109 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640201","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}
引用次数: 0
Microtubule nucleation: How the NEDD1:MZT1:GCP3 trio captures the γ-TuRC. 微管成核:NEDD1:MZT1:GCP3三人组如何捕获γ-TuRC。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-15 DOI: 10.1083/jcb.202506019
Clémence Paumier,Cécile Sauvanet,Benoît Gigant
{"title":"Microtubule nucleation: How the NEDD1:MZT1:GCP3 trio captures the γ-TuRC.","authors":"Clémence Paumier,Cécile Sauvanet,Benoît Gigant","doi":"10.1083/jcb.202506019","DOIUrl":"https://doi.org/10.1083/jcb.202506019","url":null,"abstract":"In the cell, microtubules are nucleated by the γ-tubulin ring complex (γ-TuRC). In this issue, Muñoz-Hernández, Xu, and colleagues (https://doi.org/10.1083/jcb.202410206) combine cryo-EM and AlphaFold modeling to detail how the NEDD1 protein recruits the γ-TuRC to microtubule-organizing centers.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"94 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630461","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}
引用次数: 0
Myosin 15 participates in assembly and remodeling of the presynapse. 肌凝蛋白15参与突触前的组装和重塑。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-08 DOI: 10.1083/jcb.202305059
Astrid G Petzoldt,Marc J F Escher,Oriane Turrel,Niclas Gimber,Ina M Schedina,Sophie Walter,Torsten W B Götz,Marta Maglione,David Toppe,Tanja Matkovic-Rachid,Alexander Neumann,Janine Lützkendorf,Jan Schmoranzer,Martin Lehmann,Jörg Großhans,Stephan J Sigrist
{"title":"Myosin 15 participates in assembly and remodeling of the presynapse.","authors":"Astrid G Petzoldt,Marc J F Escher,Oriane Turrel,Niclas Gimber,Ina M Schedina,Sophie Walter,Torsten W B Götz,Marta Maglione,David Toppe,Tanja Matkovic-Rachid,Alexander Neumann,Janine Lützkendorf,Jan Schmoranzer,Martin Lehmann,Jörg Großhans,Stephan J Sigrist","doi":"10.1083/jcb.202305059","DOIUrl":"https://doi.org/10.1083/jcb.202305059","url":null,"abstract":"The assembly and remodeling of presynaptic specializations are of crucial importance for circuit development and adaptive behaviors. However, the mechanisms by which presynaptic material is locally distributed within synaptic terminals and across consuming active zones remain poorly understood. In this study, we identify the conserved unconventional class XV myosin, Myo15, an actin motor, as a novel regulator of presynaptic assembly and remodeling in Drosophila. Myo15 localizes to the local actin and microtubule network at synaptic terminals. Depletion of Myo15 resulted in smaller individual active zones, increased active zone density, and irregular terminal morphology, while its overexpression enlarged individual active zones and promoted synaptic terminal growth. Myo15 was found to modulate the actin meshwork, and deletion of its microtubule-binding MyTH4 domain rendered the protein nonfunctional. Furthermore, Myo15 was essential for presynaptic functional homeostatic plasticity and memory consolidation. These findings suggest that Myo15 plays a critical role in the assembly and remodeling of presynaptic active zones.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"47 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578795","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}
引用次数: 0
Pex30-dependent membrane contact sites maintain ER lipid homeostasis. pex30依赖的膜接触位点维持内质网脂质稳态。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-05-23 DOI: 10.1083/jcb.202409039
Joana Veríssimo Ferreira, Yara Ahmed, Tiaan Heunis, Aamna Jain, Errin Johnson, Markus Räschle, Robert Ernst, Stefano Vanni, Pedro Carvalho
{"title":"Pex30-dependent membrane contact sites maintain ER lipid homeostasis.","authors":"Joana Veríssimo Ferreira, Yara Ahmed, Tiaan Heunis, Aamna Jain, Errin Johnson, Markus Räschle, Robert Ernst, Stefano Vanni, Pedro Carvalho","doi":"10.1083/jcb.202409039","DOIUrl":"10.1083/jcb.202409039","url":null,"abstract":"<p><p>In eukaryotic cells, communication between organelles and the coordination of their activities depend on membrane contact sites (MCS). How MCS are regulated under the dynamic cellular environment remains poorly understood. Here, we investigate how Pex30, a membrane protein localized to the endoplasmic reticulum (ER), regulates multiple MCS in budding yeast. We show that Pex30 is critical for the integrity of ER MCS with peroxisomes and vacuoles. This requires the dysferlin (DysF) domain on the Pex30 cytosolic tail. This domain binds to phosphatidic acid (PA) both in vitro and in silico, and it is important for normal PA metabolism in vivo. The DysF domain is evolutionarily conserved and may play a general role in PA homeostasis across eukaryotes. We further show that the ER-vacuole MCS requires a Pex30 C-terminal domain of unknown function and that its activity is controlled by phosphorylation in response to metabolic cues. These findings provide new insights into the dynamic nature of MCS and their coordination with cellular metabolism.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 7","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127381","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}
引用次数: 0
Retinal ganglion cell migration and viability requires the kinase LKB1. 视网膜神经节细胞的迁移和生存需要LKB1激酶。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-06-11 DOI: 10.1083/jcb.202410023
Robert D Mackin, Ritika V Bhalla, Viktor Akhanov, Qudrat T Abdulwahab, Courtney A Burger, Melanie A Samuel
{"title":"Retinal ganglion cell migration and viability requires the kinase LKB1.","authors":"Robert D Mackin, Ritika V Bhalla, Viktor Akhanov, Qudrat T Abdulwahab, Courtney A Burger, Melanie A Samuel","doi":"10.1083/jcb.202410023","DOIUrl":"10.1083/jcb.202410023","url":null,"abstract":"<p><p>The arrangement of neurons into ordered layers underlies circuit function in many nervous system regions. This is particularly true in the mammalian retina. Here, fate-committed retinal ganglion cells (RGCs) migrate from the apical to the inner retina, where they form connections that enable vision. The mechanisms that permit ganglion cell migration and whether distinct ganglion cell types use different migration modes are unknown. We show that the serine/threonine kinase LKB1 regulates ganglion cell migration and nuclear positioning. In the absence of LKB1, many ganglion cells remain in the apical retina. Misplaced cells show modified morphologies and display altered cytoskeletal proteins. Examination of RGC types revealed that LKB1 is specifically required to promote F-type RGC (F-RGC) migration. The failure of F-RGCs to migrate results in a significant F-RGC loss via increased cell death and microglia engulfment. Together, these results identify molecular determinates of ganglion cell migration and indicate that different ganglion cell types can use distinct programs to ensure their localization.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 7","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266327","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}
引用次数: 0
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