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Acetic acid-induced stress granules function as scaffolding complexes for Hog1 activation by Pbs2. 醋酸诱导的应激颗粒是Pbs2激活Hog1的支架复合物。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-11 DOI: 10.1083/jcb.202409072
Jongmin Lee, Kazuo Tatebayashi, David E Levin
{"title":"Acetic acid-induced stress granules function as scaffolding complexes for Hog1 activation by Pbs2.","authors":"Jongmin Lee, Kazuo Tatebayashi, David E Levin","doi":"10.1083/jcb.202409072","DOIUrl":"10.1083/jcb.202409072","url":null,"abstract":"<p><p>Stress-activated protein kinases (SAPKs) respond to a wide variety of stressors. In most cases, the pathways through which specific stress signals are transmitted to the SAPK are not known. We show that the yeast SAPK Hog1 is activated by acetic acid through an intracellular mechanism that does not involve stimulation of the high osmolarity glycerol (HOG) signaling pathway beyond its basal level. Rather, acetic acid treatment drives the formation of stress granules, which function as a scaffold to bring Hog1 together with Pbs2, its immediately upstream activating kinase, in a stable assembly that leverages the basal activity of Pbs2 to phosphorylate Hog1. Deletion analysis of stress granule components revealed that the assembly is critical for both the acetic acid-induced activation of Hog1 and its association with Pbs2. Activated Hog1 remains associated with stress granules, which may have implications for its targeting.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605029","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
Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity. 神经酰胺通过调节膜流动性介导细胞间内质网应力传递。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-26 DOI: 10.1083/jcb.202405060
Yazhen Huo, Xinlu Liu, Chen Lu, Tao Li, Zaili Yang, Fenfen Xu, Si Chen, Kailin Yin, Likun Wang
{"title":"Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity.","authors":"Yazhen Huo, Xinlu Liu, Chen Lu, Tao Li, Zaili Yang, Fenfen Xu, Si Chen, Kailin Yin, Likun Wang","doi":"10.1083/jcb.202405060","DOIUrl":"10.1083/jcb.202405060","url":null,"abstract":"<p><p>Under endoplasmic reticulum (ER) stress (ERS), cells initiate the unfolded protein response (UPR) to maintain ER homeostasis. Recent studies revealed ERS transmission between cells and tissues, by activating the cell-nonautonomous UPR in cells that do not experience ERS directly. Here, we report that ERS triggers a rapid release of ceramide independent of the UPR, but requiring the acid sphingomyelinase activity. Carried by lipoproteins, ceramide is delivered to receiving cells to induce the UPR and regulate cell functions at multiple aspects, including lipid accumulation, cell death, and cytokine production. Mechanistically, extracellular ceramide stimulates ceramide synthesis at the transcription level in receiving cells, leading to ceramide accumulation in the ER so as to reduce membrane fluidity to disrupt ER calcium homeostasis, thus activating the UPR. Sphingomyelin counterbalanced the effect of ceramide. UPR induction is the frontline response to protect cells from ceramide insult. Our study suggests ceramide-mediated ERS transmission as a universal cell-cell communication model regulating a wide range of physiological events.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709927","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
Interactions with multiple inner kinetochore proteins determine mitotic localization of FACT. 与多个内着丝点蛋白的相互作用决定了FACT的有丝分裂定位。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-17 DOI: 10.1083/jcb.202412042
Julia Schweighofer, Bhagyashree Mulay, Ingrid Hoffmann, Doro Vogt, Marion E Pesenti, Andrea Musacchio
{"title":"Interactions with multiple inner kinetochore proteins determine mitotic localization of FACT.","authors":"Julia Schweighofer, Bhagyashree Mulay, Ingrid Hoffmann, Doro Vogt, Marion E Pesenti, Andrea Musacchio","doi":"10.1083/jcb.202412042","DOIUrl":"10.1083/jcb.202412042","url":null,"abstract":"<p><p>The FAcilitates Chromatin Transcription (FACT) complex is a dimeric histone chaperone that operates on chromatin during transcription and replication. FACT also interacts with a specialized centromeric nucleosome containing the histone H3 variant centromere protein A (CENP-A) and with CENP-TW, two subunits of the constitutive centromere-associated network (CCAN), a 16-protein complex associated with CENP-A. The significance of these interactions remains elusive. Here, we show that FACT has multiple additional binding sites on CCAN. The interaction with CCAN is strongly stimulated by casein kinase II phosphorylation of FACT. Mitotic localization of FACT to kinetochores is strictly dependent on specific CCAN subcomplexes. Conversely, CENP-TW requires FACT for stable localization. Unexpectedly, we also find that DNA readily displaces FACT from CCAN, supporting the speculation that FACT becomes recruited through a pool of CCAN that is not stably integrated into chromatin. Collectively, our results point to a potential role of FACT in chaperoning CCAN during transcription or in the stabilization of CCAN at the centromere during the cell cycle.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648577","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
Cell signaling facilitates apical constriction by basolaterally recruiting Arp2/3 via Rac and WAVE. 细胞信号通过Rac和WAVE向基底侧募集Arp2/3促进根尖收缩。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-05 DOI: 10.1083/jcb.202409133
Pu Zhang, Taylor N Medwig-Kinney, Eleanor A Breiner, Jadyn M Perez, April N Song, Bob Goldstein
{"title":"Cell signaling facilitates apical constriction by basolaterally recruiting Arp2/3 via Rac and WAVE.","authors":"Pu Zhang, Taylor N Medwig-Kinney, Eleanor A Breiner, Jadyn M Perez, April N Song, Bob Goldstein","doi":"10.1083/jcb.202409133","DOIUrl":"10.1083/jcb.202409133","url":null,"abstract":"<p><p>Apical constriction is a critical cell shape change that drives cell internalization and tissue bending. How precisely localized actomyosin regulators drive apical constriction remains poorly understood. Caenorhabditis elegans gastrulation provides a valuable model to address this question. The Arp2/3 complex is essential in C. elegans gastrulation. To understand how Arp2/3 is locally regulated, we imaged embryos with endogenously tagged Arp2/3 and its nucleation-promoting factors (NPFs). The three NPFs-WAVE, WASP, and WASH-controlled Arp2/3 localization at distinct subcellular locations. We exploited this finding to study distinct populations of Arp2/3 and found that only WAVE depletion caused penetrant gastrulation defects. WAVE localized basolaterally with Arp2/3 and controlled F-actin levels near cell-cell contacts. WAVE and Arp2/3 localization depended on CED-10/Rac. Establishing ectopic cell contacts recruited WAVE and Arp2/3, identifying the contact as a symmetry-breaking cue for localization of these proteins. These results suggest that cell-cell signaling via Rac activates WAVE and Arp2/3 basolaterally and that basolateral Arp2/3 makes an important contribution to apical constriction.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556962","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
Dock1 functions in Schwann cells to regulate development, maintenance, and repair. Dock1在雪旺细胞中起调节发育、维持和修复的作用。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-19 DOI: 10.1083/jcb.202311041
Ryan A Doan, Kelly R Monk
{"title":"Dock1 functions in Schwann cells to regulate development, maintenance, and repair.","authors":"Ryan A Doan, Kelly R Monk","doi":"10.1083/jcb.202311041","DOIUrl":"10.1083/jcb.202311041","url":null,"abstract":"<p><p>Schwann cells, the myelinating glia of the peripheral nervous system (PNS), are critical for myelin development, maintenance, and repair. Rac1 is a known regulator of radial sorting, a key step in developmental myelination. Previously, in zebrafish, we showed that the loss of Dock1, a Rac1-specific guanine nucleotide exchange factor, resulted in delayed peripheral myelination during development. Here, we demonstrate that Dock1 is necessary for myelin maintenance and remyelination after injury in adult zebrafish. Furthermore, Dock1 performs an evolutionarily conserved role in mice, functioning cell autonomously in Schwann cells to regulate the development, maintenance, and repair of peripheral myelin. Pharmacological and genetic manipulation of Rac1 in larval zebrafish, along with the analysis of active Rac1 levels in developing Dock1 mutant mouse nerves, revealed an interaction between these two proteins. We propose that the interplay between Dock1 and Rac1 signaling in Schwann cells is required to establish, maintain, and facilitate repair and remyelination within the PNS.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656711","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
TANGO2 is an acyl-CoA binding protein. TANGO2是一种酰基辅酶a结合蛋白。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-02-27 DOI: 10.1083/jcb.202410001
Agustin Leonardo Lujan, Ombretta Foresti, Jose Wojnacki, Gonzalo Bigliani, Nathalie Brouwers, Maria Jesus Pena, Stefania Androulaki, Tomomi Hashidate-Yoshida, Maria Kalyukina, Sergey S Novoselov, Hideo Shindou, Vivek Malhotra
{"title":"TANGO2 is an acyl-CoA binding protein.","authors":"Agustin Leonardo Lujan, Ombretta Foresti, Jose Wojnacki, Gonzalo Bigliani, Nathalie Brouwers, Maria Jesus Pena, Stefania Androulaki, Tomomi Hashidate-Yoshida, Maria Kalyukina, Sergey S Novoselov, Hideo Shindou, Vivek Malhotra","doi":"10.1083/jcb.202410001","DOIUrl":"10.1083/jcb.202410001","url":null,"abstract":"<p><p>Loss of TANGO2 in humans precipitates metabolic crises during periods of heightened energy demand, such as fasting, infections, or high fever. TANGO2 has been implicated in various functions, including lipid metabolism and heme transport, and its cellular localization remains uncertain. In our study, we demonstrate that TANGO2 localizes to the mitochondrial lumen via a structural region containing LIL residues. Mutations in these LIL residues cause TANGO2 to relocate to the periphery of lipid droplets. We further show that purified TANGO2 binds acyl-coenzyme A, and mutations in the highly conserved NRDE sequence of TANGO2 inhibit this binding. Collectively, our findings suggest that TANGO2 serves as an acyl-coenzyme A binding protein. These insights may provide new avenues for addressing the severe cardiomyopathies and rhabdomyolysis associated with defective TANGO2 in humans.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523521","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
Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors. Ca2+结合Esyt调节果蝇光感受器膜接触位点密度。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-05 DOI: 10.1083/jcb.202407190
Vaisaly R Nath, Harini Krishnan, Shirish Mishra, Padinjat Raghu
{"title":"Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors.","authors":"Vaisaly R Nath, Harini Krishnan, Shirish Mishra, Padinjat Raghu","doi":"10.1083/jcb.202407190","DOIUrl":"10.1083/jcb.202407190","url":null,"abstract":"<p><p>Membrane contact sites (MCS) between the plasma membrane (PM) and endoplasmic reticulum (ER) regulate Ca2+ influx. However, the mechanisms by which cells modulate ER-PM MCS density are not understood, and the role of Ca2+, if any, in regulating these is unknown. We report that in Drosophila photoreceptors, MCS density is regulated by the Ca2+ channels, TRP and TRPL. Regulation of MCS density by Ca2+ is mediated by Drosophila extended synaptotagmin (dEsyt), a protein localized to ER-PM MCS and previously shown to regulate MCS density. We find that the Ca2+-binding activity of dEsyt is required for its function in vivo. dEsytCaBM, a Ca2+ non-binding mutant of dEsyt is unable to modulate MCS structure. Further, reconstitution of dEsyt null photoreceptors with dEsytCaBM is unable to rescue ER-PM MCS density and other key phenotypes. Thus, our data supports a role for Ca2+ binding to dEsyt in regulating ER-PM MCS density in photoreceptors thus tuning signal transduction during light-activated Ca2+ influx.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556957","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
Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers. 通过破坏早期乳腺癌中CIZ1-RNA核组装的表观遗传去编程。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-11 DOI: 10.1083/jcb.202409123
Gabrielle L Turvey, Ernesto López de Alba, Emma Stewart, Heather Cook, Ahmad Alalti, Richard T Gawne, Justin F-X Ainscough, Andrew S Mason, Dawn Coverley
{"title":"Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers.","authors":"Gabrielle L Turvey, Ernesto López de Alba, Emma Stewart, Heather Cook, Ahmad Alalti, Richard T Gawne, Justin F-X Ainscough, Andrew S Mason, Dawn Coverley","doi":"10.1083/jcb.202409123","DOIUrl":"10.1083/jcb.202409123","url":null,"abstract":"<p><p>CIZ1 is part of the RNA-dependent supramolecular assemblies that form around the inactive X-chromosome (Xi) in female cells and smaller assemblies throughout the nucleus in both sexes. Here, we show that CIZ1 C-terminal anchor domain (AD) is elevated in human breast tumor transcriptomes, even at stage I. Elevation correlates with deprotection of chromatin and upregulation of lncRNA-containing gene clusters in ∼10 Mb regions enriched in cancer-associated genes. We modeled the effect of AD on endogenous CIZ1-Xi assemblies and observed dominant-negative interference with their reformation after mitosis, leading to abnormal assemblies similar to those in breast cancer cells, and depletion of H2AK119ub1, H3K27me3, and Xist. Consistent alterations in gene expression were evident across the genome, showing that AD-mediated interference has a destabilizing effect, likely by unscheduled exposure of underlying chromatin to modifying enzymes. The data argue for a dominant, potent, and rapid effect of CIZ1 AD that can deprogram gene expression patterns and which may predispose incipient tumors to epigenetic instability.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605050","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
TMBIM-2 orchestrates systemic mitochondrial stress response via facilitating Ca2+ oscillations. TMBIM-2通过促进Ca2+振荡协调全身性线粒体应激反应。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-18 DOI: 10.1083/jcb.202408050
Jiasheng Li, Jimeng Cui, Xinyu Li, Di Zhu, Zhenhua Chen, Xiahe Huang, Yingchun Wang, Qingfeng Wu, Ye Tian
{"title":"TMBIM-2 orchestrates systemic mitochondrial stress response via facilitating Ca2+ oscillations.","authors":"Jiasheng Li, Jimeng Cui, Xinyu Li, Di Zhu, Zhenhua Chen, Xiahe Huang, Yingchun Wang, Qingfeng Wu, Ye Tian","doi":"10.1083/jcb.202408050","DOIUrl":"10.1083/jcb.202408050","url":null,"abstract":"<p><p>Neuronal mitochondrial function is critical for orchestrating inter-tissue communication essential for overall fitness. Despite its significance, the molecular mechanism underlying the impact of prolonged mitochondrial stresses on neuronal activity and how they orchestrate metabolism and aging remains elusive. Here, we identified the evolutionarily conserved transmembrane protein XBX-6/TMBIM-2 as a key mediator in the neuronal-to-intestinal mitochondrial unfolded protein response (UPRmt). Our investigations reveal that intrinsic neuronal mitochondrial stress triggers spatiotemporal Ca2+ oscillations in a TMBIM-2-dependent manner through the Ca2+ efflux pump MCA-3. Notably, persistent Ca2+ oscillations at synapses of ADF neurons are critical for facilitating serotonin release and the subsequent activation of the neuronal-to-intestinal UPRmt. TMBIM2 expression diminishes with age; however, its overexpression counteracts the age-related decline in aversive learning behavior and extends the lifespan of Caenorhabditis elegans. These findings underscore the intricate integration of chronic neuronal mitochondrial stress into neurotransmission processes via TMBIM-2-dependent Ca2+ equilibrium, driving metabolic adaptation and behavioral changes for the regulation of aging.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656728","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 pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network. 非常规蛋白分泌途径涉及CUPS和修饰的反式高尔基网络。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-02-27 DOI: 10.1083/jcb.202312120
Amy J Curwin, Kazuo Kurokawa, Gonzalo Bigliani, Nathalie Brouwers, Akihiko Nakano, Vivek Malhotra
{"title":"The pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network.","authors":"Amy J Curwin, Kazuo Kurokawa, Gonzalo Bigliani, Nathalie Brouwers, Akihiko Nakano, Vivek Malhotra","doi":"10.1083/jcb.202312120","DOIUrl":"10.1083/jcb.202312120","url":null,"abstract":"<p><p>Compartment for unconventional protein secretion (CUPS), a compartment for secretion of signal sequence-lacking proteins, forms through COPI-independent extraction of membranes from early Golgi cisternae, lacks Golgi-specific glycosyltransferases, and requires phosphatidylinositol 4-phosphate (PI4P) for biogenesis, as well as phosphatidylinositol 3-phosphate for stability. Our findings demonstrate that Drs2, a PI4P effector from the trans-Golgi network (TGN), is essential for CUPS formation, specifically through its interaction with Rcy1, and Rcy1 is crucial for the unconventional secretion. Using 4D super-resolution confocal live imaging microscopy, we observed that CUPS interact with a modified TGN that contains Drs2 in addition to proteins Tlg2 and Snc2, which are necessary for membrane fusion. Notably, while CUPS remain stable, the modified TGN undergoes remodeling during the later stages of unconventional secretion. In summary, we suggest that CUPS and the modified TGN, without the function of COPII and COPI, participate in collecting and sorting unconventionally secreted proteins, reflecting the role of Golgi membranes in receiving cargo from the ER during conventional secretion.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523585","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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