Journal of Cell Biology最新文献

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A collagen IV fluorophore knock-in toolkit reveals trimer diversity in C. elegans basement membranes.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-18 DOI: 10.1083/jcb.202412118
Sandhya Srinivasan, William Ramos-Lewis, Mychel R P T Morais, Qiuyi Chi, Adam W J Soh, Emily Williams, Rachel Lennon, David R Sherwood
{"title":"A collagen IV fluorophore knock-in toolkit reveals trimer diversity in C. elegans basement membranes.","authors":"Sandhya Srinivasan, William Ramos-Lewis, Mychel R P T Morais, Qiuyi Chi, Adam W J Soh, Emily Williams, Rachel Lennon, David R Sherwood","doi":"10.1083/jcb.202412118","DOIUrl":"10.1083/jcb.202412118","url":null,"abstract":"<p><p>The type IV collagen triple helix, composed of three ⍺-chains, is a core basement membrane (BM) component that assembles into a network within BMs. Endogenous tagging of all ⍺-chains with genetically encoded fluorophores has remained elusive, limiting our understanding of this crucial BM component. Through genome editing, we show that the C termini of the C. elegans type IV collagen ⍺-chains EMB-9 and LET-2 can be fused to a variety of fluorophores to create a strain toolkit with wild-type health. Using quantitative imaging, our results suggest a preference for LET-2-LET-2-EMB-9 trimer construction, but also tissue-specific flexibility in trimers assembled driven by differences in ⍺-chain expression levels. By tagging emb-9 and let-2 mutants that model human Gould syndrome, a complex multitissue disorder, we further discover defects in extracellular accumulation and turnover that might help explain disease pathology. Together, our findings identify a permissive tagging site in C. elegans that will allow diverse studies on type IV collagen regulation and function in animals.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656812","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 postsynaptic density in excitatory synapses is composed of clustered, heterogeneous nanoblocks.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-27 DOI: 10.1083/jcb.202406133
Rong Sun, James P Allen, Zhuqing Mao, Liana Wilson, Mariam Haider, Baris Alten, Zimeng Zhou, Xinyi Wang, Qiangjun Zhou
{"title":"The postsynaptic density in excitatory synapses is composed of clustered, heterogeneous nanoblocks.","authors":"Rong Sun, James P Allen, Zhuqing Mao, Liana Wilson, Mariam Haider, Baris Alten, Zimeng Zhou, Xinyi Wang, Qiangjun Zhou","doi":"10.1083/jcb.202406133","DOIUrl":"10.1083/jcb.202406133","url":null,"abstract":"<p><p>The nanoscale organization of proteins within synapses is critical for maintaining and regulating synaptic transmission and plasticity. Here, we used cryo-electron tomography (cryo-ET) to directly visualize the three-dimensional architecture and supramolecular organization of postsynaptic components in both synaptosomes and synapses from cultured neurons. Cryo-ET revealed that postsynaptic density (PSD) is composed of membrane-associated nanoblocks of various sizes. Subtomogram averaging from synaptosomes showed two types (type A and B) of postsynaptic receptor-like particles at resolutions of 24 and 26 Å, respectively. Furthermore, our analysis suggested that potential presynaptic release sites are closer to nanoblocks with type A/B receptor-like particles than to nanoblocks without type A/B receptor-like particles. The results of this study provide a more comprehensive understanding of synaptic ultrastructure and suggest that PSD is composed of clustering of various nanoblocks. These nanoblocks are heterogeneous in size, assembly, and distribution, which likely contribute to the dynamic nature of PSD in modulating synaptic strength.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719375","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 Abelson kinase and the Nedd4 family E3 ligases co-regulate Notch trafficking to limit signaling.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-04-04 DOI: 10.1083/jcb.202407066
Julio Miranda-Alban, Nicelio Sanchez-Luege, Fernando M Valbuena, Chyan Rangel, Ilaria Rebay
{"title":"The Abelson kinase and the Nedd4 family E3 ligases co-regulate Notch trafficking to limit signaling.","authors":"Julio Miranda-Alban, Nicelio Sanchez-Luege, Fernando M Valbuena, Chyan Rangel, Ilaria Rebay","doi":"10.1083/jcb.202407066","DOIUrl":"https://doi.org/10.1083/jcb.202407066","url":null,"abstract":"<p><p>Precise output from the conserved Notch signaling pathway governs a plethora of cellular processes and developmental transitions. Unlike other pathways that use a cytoplasmic relay, the Notch cell surface receptor transduces signaling directly to the nucleus, with endocytic trafficking providing critical regulatory nodes. Here we report that the cytoplasmic tyrosine kinase Abelson (Abl) facilitates Notch internalization into late endosomes/multivesicular bodies (LEs), thereby limiting signaling output in both ligand-dependent and -independent contexts. Abl phosphorylates the PPxY motif within Notch, a molecular target for its degradation via Nedd4 family ubiquitin ligases. We show that Su(dx), a family member, mediates the Abl-directed LE regulation of Notch via the PPxY, while another family member, Nedd4Lo, contributes to Notch internalization into LEs through both PPxY-dependent and -independent mechanisms. Our findings demonstrate how a network of posttranslational modifiers converging at LEs cooperatively modulates Notch signaling to ensure the precision and robustness of its cellular and developmental functions.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780020","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
An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-26 DOI: 10.1083/jcb.202408158
Joshua G Pemberton, Isobel Barlow-Busch, Meredith L Jenkins, Matthew A H Parson, Farkas Sarnyai, Seyma Nur Bektas, Yeun Ju Kim, John E Heuser, John E Burke, Tamas Balla
{"title":"An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate.","authors":"Joshua G Pemberton, Isobel Barlow-Busch, Meredith L Jenkins, Matthew A H Parson, Farkas Sarnyai, Seyma Nur Bektas, Yeun Ju Kim, John E Heuser, John E Burke, Tamas Balla","doi":"10.1083/jcb.202408158","DOIUrl":"10.1083/jcb.202408158","url":null,"abstract":"<p><p>Phosphatidylinositol (PI) 3,5-bisphosphate (PI(3,5)P2) is a minor inositol-containing phospholipid that serves as an important regulator of endolysosomal functions. However, the precise sites of subcellular enrichment and molecular targets of this regulatory lipid are poorly understood. Here, we describe the generation and detailed characterization of a short engineered catalytic fragment of the human PIKfyve enzyme, which potently converts PI 3-phosphate to PI(3,5)P2. This novel tool allowed for the evaluation of reported PI(3,5)P2-sensitive biosensors and showed that the recently identified phox homology (PX) domain of the Dictyostelium discoideum (Dd) protein, SNXA, can be used to monitor the production of PI(3,5)P2 in live cells. Modification and adaptation of the DdSNXAPX-based probes into compartment-specific bioluminescence resonance energy transfer-based biosensors allows for the real-time monitoring of PI(3,5)P2 generation within the endocytic compartments of entire cell populations. Collectively, these molecular tools should allow for exciting new studies to better understand the cellular processes controlled by localized PI(3,5)P2 metabolism.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730234","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
Structural characterization and inhibition of the interaction between ch-TOG and TACC3.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-19 DOI: 10.1083/jcb.202407002
James Shelford, Selena G Burgess, Elena Rostkova, Mark W Richards, Gabrielle Larocque, Josephina Sampson, Christian Tiede, Alistair J Fielding, Tina Daviter, Darren C Tomlinson, Antonio N Calabrese, Mark Pfuhl, Richard Bayliss, Stephen J Royle
{"title":"Structural characterization and inhibition of the interaction between ch-TOG and TACC3.","authors":"James Shelford, Selena G Burgess, Elena Rostkova, Mark W Richards, Gabrielle Larocque, Josephina Sampson, Christian Tiede, Alistair J Fielding, Tina Daviter, Darren C Tomlinson, Antonio N Calabrese, Mark Pfuhl, Richard Bayliss, Stephen J Royle","doi":"10.1083/jcb.202407002","DOIUrl":"10.1083/jcb.202407002","url":null,"abstract":"<p><p>The mitotic spindle is a bipolar array of microtubules, radiating from the poles which each contain a centrosome, embedded in pericentriolar material. Two proteins, ch-TOG and TACC3, have multiple functions at the mitotic spindle due to operating either alone, together, or in complex with other proteins. To distinguish these activities, we need new molecular tools to dissect their function. Here, we present the structure of the α-helical bundle domain of ch-TOG that mediates its interaction with TACC3 and a structural model describing the interaction, supported by biophysical and biochemical data. We have isolated Affimer tools to precisely target the ch-TOG-binding site on TACC3 in live cells, which displace ch-TOG without affecting the spindle localization of other protein complex components. Inhibition of the TACC3-ch-TOG interaction led unexpectedly to fragmentation of the pericentriolar material in metaphase cells and delayed mitotic progression, uncovering a novel role of TACC3-ch-TOG in maintaining pericentriolar material integrity during mitosis to ensure timely cell division.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656930","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
Importin-9 and a TPR domain protein MpH drive periodic patterning of ciliary arrays in Tetrahymena.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-28 DOI: 10.1083/jcb.202409057
Anushi Suwaneththiya Deraniyagala, Wolfgang Maier, Mireya Parra, Elise Nanista, Deborah Oluwabukola Sowunmi, Michael Hassan, Nathan Chasen, Sunita Sharma, Karl F Lechtreck, Eric S Cole, Natalia Bernardes, Yuh Min Chook, Jacek Gaertig
{"title":"Importin-9 and a TPR domain protein MpH drive periodic patterning of ciliary arrays in Tetrahymena.","authors":"Anushi Suwaneththiya Deraniyagala, Wolfgang Maier, Mireya Parra, Elise Nanista, Deborah Oluwabukola Sowunmi, Michael Hassan, Nathan Chasen, Sunita Sharma, Karl F Lechtreck, Eric S Cole, Natalia Bernardes, Yuh Min Chook, Jacek Gaertig","doi":"10.1083/jcb.202409057","DOIUrl":"10.1083/jcb.202409057","url":null,"abstract":"<p><p>We explored how the number of structures is determined in an intracellular organelle series. In Tetrahymena, the oral apparatus contains three diagonal ciliary rows: M1, M2, and M3. During development, the M rows emerge by sequential segmentation of a group of basal bodies, starting with the longest and most anterior M1 and ending with the shortest and most posterior M3. The mpD-1 and mpH-1 alleles increase and decrease the number of M rows, respectively. We identify MpH as a TPR protein and MpD as an importin-9. Both proteins localize to the M rows and form concentration gradients. MpH is a row elongation factor whose loss shortens all M rows and often prevents the formation of M3. MpD limits row initiation after the emergence of M2. MpD could be a part of a negative feedback loop that limits row initiation when M1 assembly is properly advanced. We conclude that the forming oral apparatus has properties of a semi-autonomous intracellular developmental field.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730249","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
Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-26 DOI: 10.1083/jcb.202408174
Jing Ze Wu, Joshua G Pemberton, Shin Morioka, Junko Sasaki, Priya Bablani, Takehiko Sasaki, Tamas Balla, Sergio Grinstein, Spencer A Freeman
{"title":"Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2.","authors":"Jing Ze Wu, Joshua G Pemberton, Shin Morioka, Junko Sasaki, Priya Bablani, Takehiko Sasaki, Tamas Balla, Sergio Grinstein, Spencer A Freeman","doi":"10.1083/jcb.202408174","DOIUrl":"10.1083/jcb.202408174","url":null,"abstract":"<p><p>Mutations or ablation of Snx10 are associated with neurodegeneration, blindness, and osteopetrosis. The similarities between osteoclasts and macrophages prompted us to analyze the role of Snx10 in phagocytosis. Deletion of Snx10 impaired phagosome resolution. Defective resolution was caused by reduced Cl- accumulation within (phago)lysosomes, replicating the phenotype reported in macrophages lacking ClC-7, a lysosomal 2Cl-/H+ antiporter. Delivery of ClC-7 to (phago)lysosomes was unaffected by ablation of Snx10, but its activity was markedly depressed. Snx10 was found to regulate ClC-7 activity indirectly by controlling the availability of phosphatidylinositol 3,5-bisphosphate (PI[3,5]P2), which inhibits ClC-7. By limiting the formation of PI(3,5)P2, Snx10 enables the accumulation of luminal Cl- in phagosomes and lysosomes, which is required for their optimal degradative function. Our data suggest that Snx10 regulates the delivery of PI 3-phosphate (PI[3]P), the precursor of PI(3,5)P2, from earlier endocytic compartments to (phago)lysosomes. By controlling the traffic of phosphoinositides, Snx10 regulates phagosomal resolution and possibly accounts for the impaired bone resorption in Snx10-deficient osteoclasts.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730257","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
Acetic acid-induced stress granules function as scaffolding complexes for Hog1 activation by Pbs2.
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
STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading.
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-21 DOI: 10.1083/jcb.202406053
Camille Rabesahala de Meritens, Amado Carreras-Sureda, Nicolas Rosa, Robert Pick, Christoph Scheiermann, Nicolas Demaurex
{"title":"STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading.","authors":"Camille Rabesahala de Meritens, Amado Carreras-Sureda, Nicolas Rosa, Robert Pick, Christoph Scheiermann, Nicolas Demaurex","doi":"10.1083/jcb.202406053","DOIUrl":"10.1083/jcb.202406053","url":null,"abstract":"<p><p>Neutrophils are highly motile leukocytes that migrate inside tissues to destroy invading pathogens. Ca2+ signals coordinate leukocytes migration, but whether Ca2+ fluxes mediated by Stim proteins at ER-PM contact sites regulate neutrophil actin-based motility is unclear. Here, we show that myeloid-specific Stim1/2 ablation decreases basal cytosolic Ca2+ levels and prevents adhesion-induced Ca2+ elevations in mouse neutrophils, reducing actin fiber formation and impairing spreading. Unexpectedly, more ER-PM contact sites were detected on the actin-poor adhesive membranes of Stim1/2-deficient neutrophils, which had reduced inositol-1,4,5-trisphosphate receptor (IP3R) immunoreactivity on confocal and immunogold micrographs despite preserved IP3R levels on western blots. Remarkably, Stim1/2-deficient neutrophils regained signaling and spreading competence in Ca2+-rich solutions and were recruited more effectively in mouse inflamed cremaster muscles in vivo. Our findings indicate that Stim1/2 preserve IP3R functionality in neutrophils, generating adhesion-dependent Ca2+ signals that control actin dynamics during neutrophil spreading. Stim proteins thus maintain IP3R signaling competence at adhesive membranes, enabling Ca2+-dependent actin remodeling during spreading in mouse neutrophils.</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/PMC11927589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673466","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.
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
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