Journal of cell science最新文献_第5页

Dachsous is a key player in epithelial wound closure through modulating cell shape changes and tissue mechanics.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-12 DOI: 10.1242/jcs.263674

Patrícia Porfírio-Rodrigues, Telmo Pereira, Antonio Jacinto, Lara Carvalho

{"title":"Dachsous is a key player in epithelial wound closure through modulating cell shape changes and tissue mechanics.","authors":"Patrícia Porfírio-Rodrigues, Telmo Pereira, Antonio Jacinto, Lara Carvalho","doi":"10.1242/jcs.263674","DOIUrl":"10.1242/jcs.263674","url":null,"abstract":"Epithelia are vital tissues in multicellular organisms, acting as barriers between external and internal environments. Simple epithelia, such as those in embryos and the adult gut, have the remarkable ability to repair wounds efficiently, making them ideal for studying epithelial repair mechanisms. In these tissues, wound closure involves the coordinated action of a contractile actomyosin cable at the wound edge and collective cell movements around the wound. However, the dynamics of cell-cell interactions during this process remain poorly understood. Here, we demonstrate that Dachsous (Ds), an atypical cadherin associated with planar cell polarity, is crucial for efficient epithelial repair in the Drosophila embryo. We show that the absence of Ds alters tissue mechanics and cell shape changes and rearrangements, leading to slower wound closure. Additionally, we reveal that occluding junctions are necessary for the proper apical localization of Ds, uncovering an unanticipated interaction between these two molecular complexes. This study identifies Ds as a novel key player in epithelial repair and highlights the need for further investigating the molecular mechanisms by which Ds modulates cell shape and tissue morphogenesis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407865","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

Potential ER tubular lumen sensing by intrinsically disordered regions.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-12 DOI: 10.1242/jcs.263696

Tomohiro Yorimitsu, Ken Sato

{"title":"Potential ER tubular lumen sensing by intrinsically disordered regions.","authors":"Tomohiro Yorimitsu, Ken Sato","doi":"10.1242/jcs.263696","DOIUrl":"10.1242/jcs.263696","url":null,"abstract":"Intrinsically disordered regions (IDRs) are known to sense the positive membrane curvature of vesicles and tubules. However, whether IDRs can sense the negative curvature of their luminal surfaces remains elusive. Here, we show that IDRs direct specific localization to endoplasmic reticulum (ER) tubules. In Saccharomyces cerevisiae, Sed4 interacts with Sec16 at the ER exit site (ERES) to promote ER export. Upon loss of this interaction, Sed4 failed to assemble at the ERES but was enriched in the ER tubules in a luminal region-dependent manner. Fusion of the Sed4 luminal region with Sec12 and Sec22, which localize throughout the ER, resulted in their enrichment in the tubules. The luminal regions of Sed4 or its homologs, predicted to be IDRs, localized to tubules when translocated alone into the ER lumen. The lumen-imported IDRs derived from cytosol-localizing Sec16 and Atg13 also exhibited tubule localization. Furthermore, Sed4 constructs in which the luminal region was replaced by these IDRs were concentrated at the ERES. Collectively, we suggest that the IDRs sense the properties of the tubule lumen, such as its surface, and facilitate Sed4 assembly at the ERES.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382586","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

Feeling the force from within - new tools and insights into nuclear mechanotransduction.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-10 DOI: 10.1242/jcs.263615

Julien Morival, Anna Hazelwood, Jan Lammerding

{"title":"Feeling the force from within - new tools and insights into nuclear mechanotransduction.","authors":"Julien Morival, Anna Hazelwood, Jan Lammerding","doi":"10.1242/jcs.263615","DOIUrl":"10.1242/jcs.263615","url":null,"abstract":"The ability of cells to sense and respond to mechanical signals is essential for many biological processes that form the basis of cell identity, tissue development and maintenance. This process, known as mechanotransduction, involves crucial feedback between mechanical force and biochemical signals, including epigenomic modifications that establish transcriptional programs. These programs, in turn, reinforce the mechanical properties of the cell and its ability to withstand mechanical perturbation. The nucleus has long been hypothesized to play a key role in mechanotransduction due to its direct exposure to forces transmitted through the cytoskeleton, its role in receiving cytoplasmic signals and its central function in gene regulation. However, parsing out the specific contributions of the nucleus from those of the cell surface and cytoplasm in mechanotransduction remains a substantial challenge. In this Review, we examine the latest evidence on how the nucleus regulates mechanotransduction, both via the nuclear envelope (NE) and through epigenetic and transcriptional machinery elements within the nuclear interior. We also explore the role of nuclear mechanotransduction in establishing a mechanical memory, characterized by a mechanical, epigenetic and transcriptomic cell state that persists after mechanical stimuli cease. Finally, we discuss current challenges in the field of nuclear mechanotransduction and present technological advances that are poised to overcome them.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585853","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

Practical recommendations for developing software for life science applications.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-17 DOI: 10.1242/jcs.263711

Joanna W Pylvänäinen, Guillaume Jacquemet, Stefania Marcotti

引用次数: 0

The non-canonical Smoothened-AMPK axis regulates Smaug1 biomolecular condensates.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-14 DOI: 10.1242/jcs.263433

María Gabriela Thomas, Ana Julia Fernández-Alvarez, Macarena Giménez, Francisco Corvetto Aristarain, Lucas Helio Cozza, Jerónimo Pimentel, João Pessoa, Malena Lucía Pascual, Lara Boscaglia, Martín Habif, Agustín Corbat, Pablo Ezequiel La Spina, Tomás Peters, Diego Martín Bustos, Maria Carmo-Fonseca, Hernán Edgardo Grecco, Graciela Lidia Boccaccio

{"title":"The non-canonical Smoothened-AMPK axis regulates Smaug1 biomolecular condensates.","authors":"María Gabriela Thomas, Ana Julia Fernández-Alvarez, Macarena Giménez, Francisco Corvetto Aristarain, Lucas Helio Cozza, Jerónimo Pimentel, João Pessoa, Malena Lucía Pascual, Lara Boscaglia, Martín Habif, Agustín Corbat, Pablo Ezequiel La Spina, Tomás Peters, Diego Martín Bustos, Maria Carmo-Fonseca, Hernán Edgardo Grecco, Graciela Lidia Boccaccio","doi":"10.1242/jcs.263433","DOIUrl":"10.1242/jcs.263433","url":null,"abstract":"Biomolecular condensates (BMCs) emerge as important players in RNA regulation. The RNA-binding protein Smaug forms cytosolic BMCs in mammals, insects and yeasts and affects mitochondrial function and/or responses to nutrient deprivation. Here, we found that the non-canonical activation of the Smoothened (SMO)-AMPK pathway, which is known to affect energy metabolism, triggers the immediate disassembly of BMCs formed by a number of human and rodent Smaug orthologs, whereas processing bodies remain rather unaltered. A non-phosphorylatable SMO mutant abrogated the effect, involving SMO phosphorylation in human (h)Smaug1 (also known as SAMD4A) BMCs regulation. Three mechanistically different SMO ligands, namely SAG, GSA-10 and cyclopamine, elicited a similar response, which was blocked upon AMPK pharmacological inhibition. Polysome disassembly by puromycin halted Smaug1 BMC dissolution, thus suggesting that unbound transcripts became translationally active. Single-molecule fluorescent in situ hybridization illustrated the release of UQCRC1 mRNA. Finally, Smaug1 is a phosphoprotein bound by 14-3-3 proteins, and the competitive inhibitor difopein blocked the response to non-canonical SMO stimulation. We propose that the regulated condensation and dispersion of Smaug1 BMCs generate translational changes that contribute to metabolic regulation downstream of the non-canonical SMO-AMPK axis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382588","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

Disruption of ER-mitochondria contact sites induces autophagy-dependent loss of P-bodies through the Ca2+-CaMKK2-AMPK pathway.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-12 DOI: 10.1242/jcs.263652

Nikhil More, Jomon Joseph

{"title":"Disruption of ER-mitochondria contact sites induces autophagy-dependent loss of P-bodies through the Ca2+-CaMKK2-AMPK pathway.","authors":"Nikhil More, Jomon Joseph","doi":"10.1242/jcs.263652","DOIUrl":"https://doi.org/10.1242/jcs.263652","url":null,"abstract":"P-bodies (PBs) and stress granules (SGs) are conserved, non-membranous cytoplasmic condensates of RNA-protein complexes. PBs are implicated in post-transcriptional regulation of gene expression through mRNA decay, translational repression and/or storage. Although much is known about the de novo formation of PBs and SGs involving liquid-liquid phase separation through multiple protein-protein and protein-RNA interactions, their subcellular localization and turnover mechanisms are less understood. Here, we report the presence of a subpopulation of PBs and SGs that are in proximity to ER-mitochondria contact sites (ERMCSs) in mammalian cells. Disruption of ERMCSs, achieved through depletion of ER-mitochondria tethering proteins, leads to the disappearance of PBs but not SGs. This effect can be reversed by inhibiting autophagy through both genetic and pharmacological means. Additionally, we find that the disruption of ERMCSs leads to cytosolic Ca2+-induced activation of CaMKK2 and AMP-activated protein kinase (AMPK), ultimately resulting in an autophagy-dependent decrease in PB abundance. Collectively, our findings unveil a mechanism wherein disturbances in ERMCSs induce autophagy-dependent loss of PBs via activation of the Ca2+-CaMKK2-AMPK pathway, thus potentially linking the dynamics and functions of ERMCS with post-transcriptional gene regulation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605084","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

Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-28 DOI: 10.1242/jcs.263846

Ilka Budde, André Schlichting, David Ing, Sandra Schimmelpfennig, Anna Kuntze, Benedikt Fels, Joelle M-J Romac, Sandip M Swain, Rodger A Liddle, Angela Stevens, Albrecht Schwab, Zoltán Pethő

{"title":"Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.","authors":"Ilka Budde, André Schlichting, David Ing, Sandra Schimmelpfennig, Anna Kuntze, Benedikt Fels, Joelle M-J Romac, Sandip M Swain, Rodger A Liddle, Angela Stevens, Albrecht Schwab, Zoltán Pethő","doi":"10.1242/jcs.263846","DOIUrl":"10.1242/jcs.263846","url":null,"abstract":"Pancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces durotaxis, a form of directional cell migration driven by differential stiffness. However, the molecular sensors behind durotaxis are still unclear. To investigate the role of mechanosensitive ion channels in PSC durotaxis, we established a two-dimensional stiffness gradient mimicking PDAC. Using pharmacological and genetic methods, we investigated the contribution of the ion channels Piezo1, TRPC1, and TRPV4 in PSC durotaxis. We found that PSC migration towards a stiffer substrate is diminished by altering Piezo1 activity. Moreover, disrupting TRPC1 along with TRPV4 abolishes PSC durotaxis even when Piezo1 is functional. Our results demonstrate that optimal PSC durotaxis requires an intermediary level of ion channel activity, which we simulated via a numerically discretized mathematical model. These findings suggest that mechanosensitive Piezo1 channels detect the differential stiffness microenvironment. The resulting intracellular signals are amplified by TRPV4 and TRPC1 channels to guide efficient PSC durotaxis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523619","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

SuperResNET - single-molecule network analysis detects changes to clathrin structure induced by small-molecule inhibitors. SuperResNET：单分子网络分析检测小分子抑制剂对凝集素结构的改变。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-20 DOI: 10.1242/jcs.263570

Timothy H Wong, Ismail M Khater, Christian Hallgrimson, Y Lydia Li, Ghassan Hamarneh, Ivan R Nabi

{"title":"SuperResNET - single-molecule network analysis detects changes to clathrin structure induced by small-molecule inhibitors.","authors":"Timothy H Wong, Ismail M Khater, Christian Hallgrimson, Y Lydia Li, Ghassan Hamarneh, Ivan R Nabi","doi":"10.1242/jcs.263570","DOIUrl":"10.1242/jcs.263570","url":null,"abstract":"SuperResNET is a network analysis pipeline for the analysis of point cloud data generated by single-molecule localization microscopy (SMLM). Here, we applied SuperResNET network analysis of SMLM direct stochastic optical reconstruction microscopy (dSTORM) data to determine how the clathrin endocytosis inhibitors pitstop 2, dynasore and latrunculin A (LatA) alter the morphology of clathrin-coated pits. SuperResNET analysis of HeLa and Cos7 cells identified three classes of clathrin structures: small oligomers (class I), pits and vesicles (class II), and larger clusters corresponding to fused pits or clathrin plaques (class III). Pitstop 2 and dynasore treatment induced distinct homogeneous populations of class II structures in HeLa cells, suggesting that they arrest endocytosis at different stages. Inhibition of endocytosis was not via actin depolymerization, as the actin-depolymerizing agent LatA induced large, heterogeneous clathrin structures. Ternary analysis of SuperResNET shape features presented a distinct more planar profile for blobs from pitstop 2-treated cells, which aligned with clathrin pits identified with high-resolution minimal photon fluxes (MINFLUX) microscopy, whereas control structures resembled MINFLUX clathrin vesicles. SuperResNET analysis therefore showed that pitstop 2 arrests clathrin pit maturation at early stages of pit formation, representing an approach to detect the effect of small molecules on target structures in situ in the cell from SMLM datasets.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046931","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

γ-secretase facilitates retromer-mediated retrograde transport.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-20 DOI: 10.1242/jcs.263538

Yuka Takeo, Mac Crite, Kashif Mehmood, Daniel DiMaio

{"title":"γ-secretase facilitates retromer-mediated retrograde transport.","authors":"Yuka Takeo, Mac Crite, Kashif Mehmood, Daniel DiMaio","doi":"10.1242/jcs.263538","DOIUrl":"10.1242/jcs.263538","url":null,"abstract":"Retromer mediates retrograde transport of protein cargoes from endosomes to the trans-Golgi network (TGN). γ-secretase is a protease that cleaves the transmembrane domain of its target proteins. Although retromer can form a stable complex with γ-secretase, the functional consequences of this interaction are not known. Here, we report that retromer-mediated retrograde protein trafficking in cultured human epithelial cells is impaired by the γ-secretase inhibitor XXI or by knockout of PS1 (also known as PSEN1), the catalytic subunit of γ-secretase. These treatments inhibited endosome-to-TGN trafficking of retromer-dependent retrograde cellular cargoes, divalent metal transporter 1 isoform II, cation-independent mannose-6-phosphate receptor and shiga toxin, whereas trafficking of retromer-independent cargoes, cholera toxin and a mutant CIMPR unable to bind retromer was not affected. Moreover, we found that γ-secretase associates with retromer cargoes even in the absence of retromer. XXI treatment and PS1 knockout did not inhibit the ability of retromer or γ-secretase to associate with cargo and did not affect the expression of retromer subunits or Rab7-GTP, which regulates retromer-cargo interaction. These results imply that the γ-secretase-retromer interaction facilitates retromer-mediated retrograde trafficking of cellular transmembrane proteins.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046940","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

The spatial choreography of mRNA biosynthesis.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-28 DOI: 10.1242/jcs.263504

André Ventura-Gomes, Maria Carmo-Fonseca

引用次数: 0