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Addendum: CYTOPLASMIC FILAMENTS OF AMOEBA PROTEUS: I. The Role of Filaments in Consistency Changes and Movement. 附录:变形变形虫的细胞质纤维:1 .纤维在一致性变化和运动中的作用。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2026-01-22 DOI: 10.1083/jcb.46.2.26701082026a
Thomas D Pollard, Susumu Ito
{"title":"Addendum: CYTOPLASMIC FILAMENTS OF AMOEBA PROTEUS: I. The Role of Filaments in Consistency Changes and Movement.","authors":"Thomas D Pollard, Susumu Ito","doi":"10.1083/jcb.46.2.26701082026a","DOIUrl":"10.1083/jcb.46.2.26701082026a","url":null,"abstract":"","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12854278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029872","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
Ist2 is a phospholipid scramblase that links lipid transport at the ER to organelle homeostasis. Ist2是一种磷脂绞合酶,将内质网的脂质转运与细胞器稳态联系起来。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2025-12-26 DOI: 10.1083/jcb.202502112
Heitor Gobbi Sebinelli, Camille Syska, Hafez Razmazma, Véronique Albanèse, Ana Rita Dias Araujo, Cecile Hilpert, Cédric Montigny, Christine Jaxel, Manuella Tchamba, Karolina Belingar, Juan Martín D'Ambrosio, Luca Monticelli, Guillaume Lenoir, Alenka Čopič
{"title":"Ist2 is a phospholipid scramblase that links lipid transport at the ER to organelle homeostasis.","authors":"Heitor Gobbi Sebinelli, Camille Syska, Hafez Razmazma, Véronique Albanèse, Ana Rita Dias Araujo, Cecile Hilpert, Cédric Montigny, Christine Jaxel, Manuella Tchamba, Karolina Belingar, Juan Martín D'Ambrosio, Luca Monticelli, Guillaume Lenoir, Alenka Čopič","doi":"10.1083/jcb.202502112","DOIUrl":"https://doi.org/10.1083/jcb.202502112","url":null,"abstract":"<p><p>Lipid scramblases allow passive flip-flop of phospholipids between bilayer leaflets, thereby promoting membrane symmetry. At the endoplasmic reticulum (ER), where phospholipid synthesis is restricted to one leaflet, scramblase activity should be essential for equilibrated membrane growth. The yeast protein Ist2 contains an ER domain and a cytosolic tail that binds the plasma membrane and participates in the transfer of phosphatidylserine. We show both in vitro and in silico that the ER domain of Ist2, which bears homology to the TMEM16 proteins, possesses a lipid scramblase activity that is not regulated by Ca2+. In cells, overexpression or deletion of the ER domain of Ist2 affects ER-related processes including COPII-mediated vesicular transport, lipid droplet homeostasis, and general phospholipid transport, with a specific contribution of residues implicated in lipid scrambling. The weak phenotypes can be augmented by the deletion of another putative scramblase, the protein insertase Get1, suggesting that the combined action of different proteins supports lipid scrambling at the ER.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878468","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
Phosphatidylserine exposure and annexin A5 weaken the actin cortex in osteoclast fusion. 磷脂酰丝氨酸暴露和膜联蛋白A5削弱了破骨细胞融合中的肌动蛋白皮质。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2025-12-02 DOI: 10.1083/jcb.202508055
Evgenia Leikina, Andrey K Tsaturyan, Kamran Melikov, Jarred M Whitlock, Jared Cunanan, Morgan Roegner, Griffin Katz, Michael M Kozlov, Leonid V Chernomordik
{"title":"Phosphatidylserine exposure and annexin A5 weaken the actin cortex in osteoclast fusion.","authors":"Evgenia Leikina, Andrey K Tsaturyan, Kamran Melikov, Jarred M Whitlock, Jared Cunanan, Morgan Roegner, Griffin Katz, Michael M Kozlov, Leonid V Chernomordik","doi":"10.1083/jcb.202508055","DOIUrl":"10.1083/jcb.202508055","url":null,"abstract":"<p><p>Diverse cell-cell fusions involve Ca2+ signaling, exposure of phosphatidylserine (PS) at the cell surface and binding of extracellular annexin A5 (Anx A5). Here we report that in the fusion stage of osteoclast formation, each of these shared hallmarks of cell fusion represents a step in a novel signaling pathway. A rise in intracellular Ca2+ activates a lipid scramblase that translocates PS from the inner to the outer leaflet of the plasma membrane. This redistribution is enhanced by binding of extracellular Anx A5 to PS. Depletion of PS in the inner leaflet weakens actin cortex-plasma membrane attachment, as evidenced by the preferential localization of the cortex detachment areas within PS-enriched regions at the cell surface. Weakening of the cortex attachment promotes osteoclast fusion. Based on these findings and theoretical analysis, we propose that PS exposure-to-cortex detachment pathway facilitates pre-fusion membrane contacts and fusion pore expansion in osteoclast fusion and other cell-cell fusions by promoting outward membrane deformations with locally elevated tension.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654416","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
Regulation of the formin INF2 by actin monomers and calcium/calmodulin. 肌动蛋白单体和钙/钙调蛋白对双胍蛋白INF2的调控。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2026-01-07 DOI: 10.1083/jcb.202507147
Miriam Lee, Aiman Jalmukhambetova, T Emme Burgin, Henry N Higgs
{"title":"Regulation of the formin INF2 by actin monomers and calcium/calmodulin.","authors":"Miriam Lee, Aiman Jalmukhambetova, T Emme Burgin, Henry N Higgs","doi":"10.1083/jcb.202507147","DOIUrl":"10.1083/jcb.202507147","url":null,"abstract":"<p><p>In response to increased intracellular calcium, the formin INF2 polymerizes 20-30% of the total cellular actin pool within 30 s, suggesting robust regulation. INF2 regulation requires an autoinhibitory interaction between the N-terminal diaphanous inhibitory domain (DID) and the C-terminal diaphanous autoregulatory domain (DAD). DID mutations are dominantly linked to two human diseases and constitutively activate INF2. However, DAD binding to actin monomers competes with DID binding, disrupting regulation. Here, we use a novel cell-free assay for the detailed investigation of INF2 regulation. Contrary to our previous findings, INF2 inhibition does not require CAP proteins but does require actin \"buffering\" by monomer-binding proteins such as profilin or thymosin. INF2 is activated by calcium-bound calmodulin (CALM) through CALM binding to the N terminus. In addition, the N terminus plays an important role in INF2 regulation beyond CALM binding. These findings support a role of actin monomer-binding proteins not only in regulating overall actin dynamics but also in specific regulation of an actin polymerization factor.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911606","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
GARLH regulates neuroligin preference for excitatory versus inhibitory synapses. GARLH调节神经素对兴奋性突触和抑制性突触的偏好。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2025-12-02 DOI: 10.1083/jcb.202507190
Tokiwa Yamasaki, Kohtarou Konno, Dilja Krueger-Burg, Yoav Noam, Nashid H Chaudhury, Megumi Morimoto-Tomita, Elizabeth J Salm, Masahiko Watanabe, Nils Brose, Susumu Tomita
{"title":"GARLH regulates neuroligin preference for excitatory versus inhibitory synapses.","authors":"Tokiwa Yamasaki, Kohtarou Konno, Dilja Krueger-Burg, Yoav Noam, Nashid H Chaudhury, Megumi Morimoto-Tomita, Elizabeth J Salm, Masahiko Watanabe, Nils Brose, Susumu Tomita","doi":"10.1083/jcb.202507190","DOIUrl":"10.1083/jcb.202507190","url":null,"abstract":"<p><p>Synaptic specificity is governed by precise combinations of cell adhesion proteins that stabilize pre- and postsynaptic sites and appropriate neurotransmitter receptors. The postsynaptic neuroligins NL1/3 and NL2/3/4 localize to excitatory and inhibitory synapses, respectively, and regulate the corresponding neurotransmitter receptors. However, the exact molecular mechanisms that determine synaptic specificity via defined combinations of neuroligins and neurotransmitter receptors remain unclear. We found that all neuroligin isoforms form a tripartite complex with GABAA receptors and GARLH4 protein, with isoform-specific preferences, and that NL1, previously thought to be restricted to excitatory synapses, is also present at inhibitory synapses. In the absence of inhibitory synapse-specific NL2/4, NL1/3 increasingly assembles with GARLH4/GABAA receptors and relocates to inhibitory synapses. Moreover, forced interaction between NL1 and GARLH4 redirects their localization to inhibitory synapses. These findings demonstrate that GARLHs regulate the synaptic specificity of neuroligins, providing the key link between neuroligins and inhibitory GABAA receptors.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654388","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
The cell biologist's guide to detecting and modulating membrane phospholipids. 细胞生物学家的指南检测和调节膜磷脂。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2026-01-02 DOI: 10.1083/jcb.202508058
Michael Worcester, Morgan M C Ricci, Claire C Weckerly, Jesus G Calixto, Gerald R V Hammond
{"title":"The cell biologist's guide to detecting and modulating membrane phospholipids.","authors":"Michael Worcester, Morgan M C Ricci, Claire C Weckerly, Jesus G Calixto, Gerald R V Hammond","doi":"10.1083/jcb.202508058","DOIUrl":"10.1083/jcb.202508058","url":null,"abstract":"<p><p>Molecular biology has benefited enormously from repurposed tools-many enzymes and antibodies evolved for other functions but are now essential for interrogating biological function by manipulating proteins or nucleic acids. In contrast, lipids have remained technically difficult to visualize or manipulate in cells. This review introduces tools that bring lipid biology into reach for molecular cell biologists, using familiar experimental approaches. We first describe adaptations of immunofluorescence and live-cell imaging of fluorescent molecules to track lipids. Then, we discuss tools for manipulating lipid levels, including pharmacologic inhibitors, synthetic biology platforms for inducible lipid generation or degradation, and optogenetic systems for precise temporal control. While some methods remain technically demanding, most tools are now broadly accessible. Our goal is to offer a practical framework for integrating lipid biology into mainstream cell biology experiments.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889317","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
DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways. dux4诱导的HSATII RNA积累驱动蛋白质聚集,影响RNA加工途径。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2025-12-02 DOI: 10.1083/jcb.202501129
Tessa Arends, Sean R Bennett, Stephen J Tapscott
{"title":"DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.","authors":"Tessa Arends, Sean R Bennett, Stephen J Tapscott","doi":"10.1083/jcb.202501129","DOIUrl":"10.1083/jcb.202501129","url":null,"abstract":"<p><p>RNA-driven protein aggregation leads to cellular dysregulation and contributes to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar RNA and human satellite II (HSATII) RNA that drive protein aggregation in muscle cells. Specifically, HSATII RNA sequesters RNA methylation factors. HSATII-YBX-1 ribonucleoprotein (RNP) complex formation is mediated by HSATII double-stranded RNA and RNA methylase NSUN2 activity. Aberrant HSATII-RNP complexes affect RNA processing pathways, including RNA splicing. Differential splicing of genes mediated by HSATII-RNP complexes is associated with pathways known to be dysregulated by DUX4 expression. These findings highlight the broader influence of DUX4 on nuclear RNA dynamics and suggest that HSATII RNA could be a critical mediator of RNA processing regulation. Understanding the impact of HSATII-RNP formation on RNA processing provides insight into the molecular mechanisms underlying FSHD.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654406","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
The traffic controller: GARLH4 dictates neuroligin synapse-type preference. 交通控制:GARLH4决定神经素突触型偏好。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2026-01-02 DOI: 10.1083/jcb.202512185
Eunjoon Kim
{"title":"The traffic controller: GARLH4 dictates neuroligin synapse-type preference.","authors":"Eunjoon Kim","doi":"10.1083/jcb.202512185","DOIUrl":"https://doi.org/10.1083/jcb.202512185","url":null,"abstract":"<p><p>Neuroligin isoforms are commonly thought to intrinsically specify synapse identity. In this issue, Yamasaki et al. (https://doi.org/10.1083/jcb.202507190) show that the auxiliary protein GARLH4 (LHFPL4) instead dictates neuroligin preference via competitive hierarchy, enabling dynamic reassignment between excitatory and inhibitory postsynaptic domains.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889274","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
Mechanically gated OSCA/TMEM63 ion channels: From physiological function to structural basis. 机械门控OSCA/TMEM63离子通道:从生理功能到结构基础。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2026-01-02 DOI: 10.1083/jcb.202507014
Siqi Deng, Qinling Qiu, Shangyu Dang, Zhiqiang Yan
{"title":"Mechanically gated OSCA/TMEM63 ion channels: From physiological function to structural basis.","authors":"Siqi Deng, Qinling Qiu, Shangyu Dang, Zhiqiang Yan","doi":"10.1083/jcb.202507014","DOIUrl":"https://doi.org/10.1083/jcb.202507014","url":null,"abstract":"<p><p>The OSCA/TMEM63 family constitutes the largest identified group of mechanically gated ion channels, having pivotal roles in cellular mechanotransduction. OSCAs are osmosensitive and mechanically gated ion channels in plants, while their animal homologs TMEM63s similarly respond to mechanical stimuli and osmotic stress, characterized by smaller conductance and higher mechanoactivation thresholds. Structural studies suggest a conserved \"force-from-lipid\" gating mechanism for the OSCA/TMEM63 family, in which membrane tension or lipid bilayer curvature directly induces conformational changes and ion conductance. This review summarizes the physiological and pathological roles of OSCA/TMEM63 proteins, highlighting potential molecular mechanisms for their roles in mechanotransduction. Based on the structural homology and functional properties in biological membranes, we proposed a mechanically gated ion channel superfamily comprising OSCA/TMEM63 and TMC proteins.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889332","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
Pexophagy meets physiology. 食腐与生理相结合。
IF 6.4 1区 生物学
Journal of Cell Biology Pub Date : 2026-02-02 Epub Date: 2025-12-29 DOI: 10.1083/jcb.202511183
Michael J Clague
{"title":"Pexophagy meets physiology.","authors":"Michael J Clague","doi":"10.1083/jcb.202511183","DOIUrl":"https://doi.org/10.1083/jcb.202511183","url":null,"abstract":"<p><p>In this issue, Xiong et al. (https://doi.org/10.1083/jcb.202503169) introduce mouse models that enable tissue-resolved mapping of peroxisome turnover and pexophagy across development, metabolism, and disease. This study reveals striking cell type-specific differences in peroxisome dynamics and establishes a versatile platform for dissecting how pexophagy integrates with mitochondrial quality control and whole-body metabolic homeostasis.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878436","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
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