Journal of cell science最新文献_第8页

The mammalian protein MTCH1 can function as an insertase. 哺乳动物蛋白MTCH1可以作为插入酶发挥作用。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 DOI: 10.1242/jcs.263736

Anna Roza Dimogkioka, Anni Elias, Doron Rapaport

{"title":"The mammalian protein MTCH1 can function as an insertase.","authors":"Anna Roza Dimogkioka, Anni Elias, Doron Rapaport","doi":"10.1242/jcs.263736","DOIUrl":"10.1242/jcs.263736","url":null,"abstract":"The outer mitochondrial membrane (OMM) hosts a variety of proteins such as import machineries, enzymes, fission and fusion factors, and pore proteins. In Saccharomyces cerevisiae, the MIM complex, consisting of Mim1 and Mim2, mediates the insertion of α-helical proteins into the OMM. Until recently, it was unclear which proteins served this function in higher eukaryotes. Recent studies have identified MTCH2 as the insertase responsible for inserting α-helical proteins into the OMM in mammals. MTCH1 is a paralogue of MTCH2 but its general function and contribution to the biogenesis process are not clear. To better characterize MTCH1, we explored whether MTCH1 or MTCH2 could functionally replace Mim1 and/or Mim2 in yeast. Expression of MTCH1 and MTCH2 in yeast cells lacking Mim1, Mim2 or both revealed that MTCH1, but not MTCH2, could compensate for the growth defects upon deleting the MIM complex. Furthermore, MTCH1 could restore the biogenesis of MIM substrates, translocase of the outer membrane (TOM) complex stability and morphology of mitochondria. These findings indicate that MTCH1, by itself, has insertase activity and is a functional equivalent for the MIM complex, despite the absence of any evolutionary relation between the mammalian and yeast insertases.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698631","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

Depletion of endomembrane reservoirs drives phagocytic appetite exhaustion in macrophages. 巨噬细胞的吞噬欲望耗竭与膜库耗竭有关。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 Epub Date: 2025-08-29 DOI: 10.1242/jcs.263539

Aaron Fountain, Mélanie Mansat, Tracy Lackraj, Maria C Gimenez, Serene Moussaoui, Maya Ezzo, Sierra Soffiaturo, Elijah Urdaneta, Munira B Verdawala, Karen Fung, Charlene Lancaster, Elliott Somerville, Boris Hinz, Mauricio R Terebiznik, Roberto J Botelho

{"title":"Depletion of endomembrane reservoirs drives phagocytic appetite exhaustion in macrophages.","authors":"Aaron Fountain, Mélanie Mansat, Tracy Lackraj, Maria C Gimenez, Serene Moussaoui, Maya Ezzo, Sierra Soffiaturo, Elijah Urdaneta, Munira B Verdawala, Karen Fung, Charlene Lancaster, Elliott Somerville, Boris Hinz, Mauricio R Terebiznik, Roberto J Botelho","doi":"10.1242/jcs.263539","DOIUrl":"10.1242/jcs.263539","url":null,"abstract":"During phagocytosis, a phagocytic cup grows via F-actin remodeling and localized secretion to entrap a particle within a phagosome, which then fuses with endosomes and lysosomes to digest the particle, followed by phagosome resolution. As spatially limited systems, phagocytes have a maximal phagocytic capacity, at which point further uptake must be reduced. However, the processes responsible for phagocytic appetite exhaustion as phagocytes reach their maximal phagocytic capacity are poorly defined. We found that macrophages at their capacity have lower surface levels of Fcγ receptors but overexpression of these receptors did not increase their capacity, suggesting that receptor levels are not limiting. We found that surface membrane in-folding, membrane tension and cortical F-actin were all reduced in exhausted macrophages. Although this might contribute to appetite suppression, we also found that 'free' endosomes and lysosomes were severely depleted in exhausted macrophages. Consequently, focal exocytosis at sites of externally bound particles was reduced. In comparison, macrophages recovered their appetite if phagosome resolution was permitted. We propose that depletion of the endomembrane pools is a major determinant of phagocytic fatigue as macrophages reach their phagocytic capacity.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753489","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 balances membrane and cortex tension to stabilize intercellular junctions and maintain the epithelial barrier. Piezo1平衡膜和皮层张力，稳定细胞间连接和维持上皮屏障。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 Epub Date: 2025-09-01 DOI: 10.1242/jcs.263938

Ahsan Javed, Aki Stubb, Clémentine Villeneuve, Satu-Marja Myllymäki, Franziska Peters, Matthias Rübsam, Carien M Niessen, Leah C Biggs, Sara A Wickström

{"title":"Piezo1 balances membrane and cortex tension to stabilize intercellular junctions and maintain the epithelial barrier.","authors":"Ahsan Javed, Aki Stubb, Clémentine Villeneuve, Satu-Marja Myllymäki, Franziska Peters, Matthias Rübsam, Carien M Niessen, Leah C Biggs, Sara A Wickström","doi":"10.1242/jcs.263938","DOIUrl":"10.1242/jcs.263938","url":null,"abstract":"Formation of the skin barrier is essential for organismal survival and tissue homeostasis. Barrier formation requires positioning of functional tight junctions (TJs) to the most suprabasal viable layer of the epidermis through a mechanical circuit that is driven by generation of high tension at adherens junctions. However, what allows the sensing of tension build-up at these adhesions and how this tension is balanced to match the requirements of tissue mechanical properties is unclear. Here, we show that the mechanosensitive ion channel Piezo1 is essential for the maturation of intercellular junctions into functional continuous adhesions. Deletion of Piezo1 results in an imbalance of cell contractility and membrane tension, leading to a delay in adhesion maturation. Consequently, the requirement for Piezo1 activity can be bypassed by lowering contractility or elevating membrane tension. In vivo, Piezo1 function in adhesion integrity becomes essential only in aged mice where alterations in tissue mechanics lead to impaired tight junctions and barrier dysfunction. Collectively these studies reveal an essential function of Piezo1 in the timely establishment and maintenance of cell-cell junctions within a mechanically tensed epidermis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753490","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

Mitochondrial protein aggregates recruit key chaperones and are sequestered in a fission- and fusion-dependent process. 线粒体蛋白聚集体招募关键伴侣，并在裂变/融合依赖的过程中被隔离。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 Epub Date: 2025-08-29 DOI: 10.1242/jcs.263680

Laura Ruland, Marc Sylvester, Lydia Maus, Hannes Beckert, Wolfgang Voos

{"title":"Mitochondrial protein aggregates recruit key chaperones and are sequestered in a fission- and fusion-dependent process.","authors":"Laura Ruland, Marc Sylvester, Lydia Maus, Hannes Beckert, Wolfgang Voos","doi":"10.1242/jcs.263680","DOIUrl":"10.1242/jcs.263680","url":null,"abstract":"The potential proteotoxicity of mitochondrial aggregates in yeast cells is reduced by a sequestration of affected polypeptides into a mitochondrial protein quality control compartment (IMiQ). Based on the expression of an aggregation-prone protein in the mitochondrial matrix, we determined the effect of organelle dynamics on aggregate sequestration. Fusion-deficient cells were unable to accumulate the aggregates in the IMiQ, resulting in a stress-sensitive phenotype. In contrast, fission-deficient cells could not separate the aggregate from the mitochondrial network. In these mitochondria, the aggregates were neutralized by the formation of a shell formed by mitochondrial chaperones. We also performed quantitative mass spectrometry to analyse the mitochondrial proteome and the extent of co-aggregation of mitochondrial proteins. Although only minor changes of the total proteome were detected in response to aggregate accumulation, we found a recruitment of proteins of the respiratory chain complexes and of the protein quality control system (PQC). In particular, members of the Hsp70 chaperone family were prominently associated with the aggregate. We conclude that this chaperone-dependent neutralization prevents a major co-aggregation of endogenous mitochondrial proteins.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742199","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

Energy deprivation in youth and old age. 青年和老年的能量剥夺。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 Epub Date: 2025-08-14 DOI: 10.1242/jcs.264018

Michael Stern

{"title":"Energy deprivation in youth and old age.","authors":"Michael Stern","doi":"10.1242/jcs.264018","DOIUrl":"10.1242/jcs.264018","url":null,"abstract":"In youth, energy deprivation primarily results from fasting. Because inconsistent nutrient availability is common for most organisms, natural selection has provided mechanisms that detect nutrient-deprived states, followed by adaptive responses that increase the likelihood of survival until nutrients are restored. Organisms respond to fasting first by oxidizing the cellular cytoplasm, then by activating redox-sensitive kinases - namely the c-Jun N-terminal kinases (henceforth collectively termed JNK) and AMP-activated protein kinase (AMPK) - and Foxo transcription factors (henceforth referred to collectively as Foxo). Together, JNK, AMPK and Foxo induce autophagy. This fasting response is beneficial because autophagy supplies substrates for metabolism that replace missing nutrients and enhances removal of damaged organelles such as mitochondria, which increases lifespan and enhances survival through the fast. Although this response is adaptive in the context of acute nutrient deprivation, it can have harmful consequences when activated chronically. Here, I propose that cells from old organisms are constitutively energy deprived because of lifetime accumulation of dysfunctional mitochondria. As a result, these cells reactivate the fasting response seen in youth. Hence, old organisms constitutively oxidize the cellular cytoplasm and activate JNK, AMPK, Foxo and, finally, autophagy. However, because energy deprivation in old age is driven by mitochondrial insufficiency rather than nutrient deprivation, this response fails to restore ATP production and becomes chronic and deleterious. I suggest that many age-related pathologies, such as oxidative stress, neurodegeneration and sarcopenia, result from aberrant activation of the fasting response.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 16","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855328","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

Somatic mutations in IRE1α regulate keratinocyte migration and survival by differentially activating Rho GTPases. IRE1α体细胞突变通过差异激活Rho gtpase调节角质形成细胞的迁移和存活。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 Epub Date: 2025-08-29 DOI: 10.1242/jcs.263790

Saie Mogre, Lily Robinson, Komal Sethia, Bipin Rimal, Jeongin Son, Christian Pacifico, Lorraine Santy, Andrew Patterson, Adam B Glick

{"title":"Somatic mutations in IRE1α regulate keratinocyte migration and survival by differentially activating Rho GTPases.","authors":"Saie Mogre, Lily Robinson, Komal Sethia, Bipin Rimal, Jeongin Son, Christian Pacifico, Lorraine Santy, Andrew Patterson, Adam B Glick","doi":"10.1242/jcs.263790","DOIUrl":"10.1242/jcs.263790","url":null,"abstract":"IRE1α is an endoplasmic reticulum (ER) transmembrane protein with cytoplasmic kinase and endoribonuclease (RNase) domains. Under ER stress, IRE1α can splice Xbp1 mRNA enabling translation of this unfolded protein response transcription factor or mediate sequence-specific degradation of mRNAs through regulated IRE1α-dependent decay (RIDD). Somatic mutations in IRE1α occur in many different human cancers including non-melanoma skin cancer (NMSC). To understand their role in skin cancer pathogenesis, we generated immortalized primary mouse keratinocytes with inducible expression of multiple engineered and cancer-associated mutations, including those present in NMSC. All NMSC mutations tested were activating mutations with elevated autophosphorylation and enhanced RIDD activity relative to the degree of change seen in Xbp1 splicing. Pathway analysis of RNA-Seq data and in vitro studies showed that RNase-impaired mutations enhanced cell migration due to increased levels of active RhoA and the RIDD target Angptl4. In contrast, activating mutations caused elevated Rac1 activation, enrichment of genes involved in DNA repair, increased phospho-ATR levels and improved survival in response to UVB irradiation, a crucial etiological factor for sun-exposure-induced skin cancers. Together, these results suggest divergent roles of IRE1α mutations that mediate crucial tumor-promoting events in keratinocytes.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626413","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

Insights into the translational activation mechanisms of the COX1 mRNA in yeast mitochondria. 酵母线粒体中COX1 mRNA翻译激活机制的研究。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 Epub Date: 2025-09-02 DOI: 10.1242/jcs.263694

Angelica Zamudio-Ochoa, Yolanda Camacho-Villasana, Ulrik Pedroza-Dávila, Aldo E García-Guerrero, Xochitl Pérez-Martínez

{"title":"Insights into the translational activation mechanisms of the COX1 mRNA in yeast mitochondria.","authors":"Angelica Zamudio-Ochoa, Yolanda Camacho-Villasana, Ulrik Pedroza-Dávila, Aldo E García-Guerrero, Xochitl Pérez-Martínez","doi":"10.1242/jcs.263694","DOIUrl":"10.1242/jcs.263694","url":null,"abstract":"Mitochondrial translation is a crucial regulatory step in mitochondrial genome expression. In Saccharomyces cerevisiae, translational activators are believed to bind to the 5' UTRs of their target mRNAs to position the mitochondrial ribosome at the start codon. Pet309 and Mss51 are translational activators of COX1 mRNA, which encodes subunit one of cytochrome c oxidase. Pet309 physically interacts with COX1 mRNA, but no direct interaction of Mss51 with its target mRNA has been detected. Currently, the mechanisms underlying translational activation of COX1, or any other mitochondrial gene, remain poorly understood. To explore in depth the mechanism of COX1 mRNA translational activation, we studied the association of Pet309 and Mss51 with the mitochondrial ribosome. Both Pet309 and Mss51 interact with the mitoribosome regardless of the presence of COX1 mRNA or of each other. The association of Pet309 with the ribosome and with COX1 mRNA depends on its N-terminal domain. These findings indicate that Pet309 and Mss51 stably interact with the mitoribosome independently of active translation. By integrating our data with previously published research, we propose a new mechanism of COX1 mRNA translation activation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 16","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955503","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

Creation and validation of a proteome-wide yeast library for protein detection and analysis. 用于蛋白质检测和分析的蛋白质组酵母文库的创建和验证。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 Epub Date: 2025-09-01 DOI: 10.1242/jcs.263848

Din Baruch, Ioannis Tsirkas, Ehud Sass, Benjamin Dubreuil, Yeynit Asraf, Amir Aharoni, Maya Schuldiner, Ofir Klein

{"title":"Creation and validation of a proteome-wide yeast library for protein detection and analysis.","authors":"Din Baruch, Ioannis Tsirkas, Ehud Sass, Benjamin Dubreuil, Yeynit Asraf, Amir Aharoni, Maya Schuldiner, Ofir Klein","doi":"10.1242/jcs.263848","DOIUrl":"10.1242/jcs.263848","url":null,"abstract":"A significant challenge in cell biology is to uncover the function of uncharacterized proteins. Surprisingly, a quarter of the proteome is still poorly understood even in the most well-studied model organisms. Systematic methodologies, including the use of tagged protein collections, have emerged as a powerful approach to address this gap. Despite the availability of proteome-wide collections featuring various fused proteins, the impact of different tags on protein function highlights the need for diversifying the tags used for functional genomic studies. To rise to this challenge, we created a proteome-wide collection of yeast strains in which proteins are N-terminally tagged with the broadly utilized and compact hemagglutinin (HA) epitope. We showcase the potential uses of our library for systematically evaluating protein size, abundance and localization using an in vivo labeling approach. Our characterization underscores the potential utility of a proteome-wide HA-tagged library in revealing novel aspects of cell biology, providing an additional powerful tool for functional genomics.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698629","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

Arsenic binds to nuclear transport factors and disrupts nucleocytoplasmic transport. 砷与核转运因子结合，破坏核细胞质转运。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-15 DOI: 10.1242/jcs.263889

Emma Lorentzon, Jongmin Lee, Jakub Masaryk, Katharina Keuenhof, Nora Karlsson, Charlotte Galipaud, Rebecca Madsen, Johanna L Höög, David E Levin, Markus J Tamás

{"title":"Arsenic binds to nuclear transport factors and disrupts nucleocytoplasmic transport.","authors":"Emma Lorentzon, Jongmin Lee, Jakub Masaryk, Katharina Keuenhof, Nora Karlsson, Charlotte Galipaud, Rebecca Madsen, Johanna L Höög, David E Levin, Markus J Tamás","doi":"10.1242/jcs.263889","DOIUrl":"10.1242/jcs.263889","url":null,"abstract":"Human exposure to arsenicals is associated with devastating diseases such as cancer and neurodegeneration. At the same time, arsenic-based drugs are used as therapeutic agents. The ability of arsenic to directly bind to proteins is correlated with its toxic and therapeutic effects, highlighting the importance of elucidating arsenic-protein interactions. In this study, we took a proteomic approach and identified 174 proteins that bind to arsenic in Saccharomyces cerevisiae. Proteins involved in nucleocytoplasmic transport were markedly enriched among the arsenic-binding proteins, and we demonstrate that arsenic binding to nuclear import factors results in their relocation from the nuclear envelope and subsequent aggregation in the cytosol. Similarly, nuclear pore proteins that make up the nuclear pore complex mislocalized and aggregated in arsenic-exposed cells. Consequently, arsenic was shown to inhibit nuclear protein import and export. We propose a model in which arsenic binding to nuclear transport factors leads to their mislocalization and aggregation, which disrupts nucleocytoplasmic transport and causes arsenic sensitivity.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731132","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

Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration. Ras-Rab5-Rac1环的前偏置激活协调了细胞的集体迁移。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-04 DOI: 10.1242/jcs.263779

Yuya Jikko, Eriko Deguchi, Kimiya Matsuda, Naoya Hino, Shinya Tsukiji, Michiyuki Matsuda, Kenta Terai

{"title":"Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration.","authors":"Yuya Jikko, Eriko Deguchi, Kimiya Matsuda, Naoya Hino, Shinya Tsukiji, Michiyuki Matsuda, Kenta Terai","doi":"10.1242/jcs.263779","DOIUrl":"10.1242/jcs.263779","url":null,"abstract":"Collective cell migration is coordinated by the front-to-rear intercellular propagation of EGFR-Ras-ERK pathway activation. However, the molecular mechanisms integrating front-to-rear information into this intercellular signaling cascade, particularly the determinants of cellular front-side specification, remain elusive. We visualized the activity of EGFR, Ras, Rac1 and Rab5A (hereafter Rab5) by using FRET biosensors and chemogenetic tools. Whereas EGFR activation was uniformly observed within cells, Ras activation was biased to the front side within cells. The polarized Ras activation depended on Merlin and Rac1, which also showed front-biased activation. Furthermore, Rab5, a crucial regulator of cell migration, demonstrated similar front-biased activation and was found to function downstream of Ras while being necessary for Rac1 activation. Thus, the positive feedback loop consisting of Ras, Rab5 and Rac1 is activated primarily at the front of collectively migrating cells. These findings offer new spatio-temporal insight into processing front-rear information during collective cell migration.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642638","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