Journal of cell science最新文献_第5页

A role for class I p21-activated kinases in the regulation of the excitability of the actin cytoskeleton. 一类p21活化激酶在肌动蛋白细胞骨架兴奋性调控中的作用。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-15 Epub Date: 2025-06-23 DOI: 10.1242/jcs.263763

Joe J Tyler, Anthony Davidson, Megan E Poxon, Montserrat Llanses Martinez, Pete Hume, Jason S King, Vassilis Koronakis

{"title":"A role for class I p21-activated kinases in the regulation of the excitability of the actin cytoskeleton.","authors":"Joe J Tyler, Anthony Davidson, Megan E Poxon, Montserrat Llanses Martinez, Pete Hume, Jason S King, Vassilis Koronakis","doi":"10.1242/jcs.263763","DOIUrl":"10.1242/jcs.263763","url":null,"abstract":"The p21-activated kinases (PAKs) are involved in a range of functions, including the regulation of the actin cytoskeleton. However, although many PAK substrates identified have been implicated in the regulation of the actin cytoskeleton, a coherent picture of the total effect of PAK activation on the state of the actin cytoskeleton is unclear. Here, we show that, in mouse embryonic fibroblasts, inhibition of class I PAK kinase activity by small-molecule inhibitors leads to the constitutive production of the phosphoinositide phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] on the ventral surface of the cell. The formation of patches of PI(3,4,5)P3 remodels the actin cytoskeleton and polarises the cell. From the overexpression of truncated and mutated PAK1 and PAK2 constructs, as well as an in vitro model of PAK activation, we propose that this is driven by a hyper recruitment of class I PAK and PAK-binding partners. This aberrant production of PI(3,4,5)P3 suggests that, by limiting its own recruitment, the kinase activity of class I PAKs acts to downregulate phosphoinositide 3-kinase (PI3K) activity, further highlighting class I PAKs as regulators of PI3K activity and therefore the excitability of the actin cytoskeleton.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368877","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

Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2. 内体RFFL泛素连接酶通过靶向Mitofusin 2调控线粒体形态。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-15 Epub Date: 2025-06-20 DOI: 10.1242/jcs.263830

Nikhil Dev Narendradev, Rishith Ravindran, Parul Jain, Shikha Chaudhary, Anoop Kumar G Velikkakath, Abyasree Sudharman, Adithya Janardhanan, Tapas Chandra Nag, Subhash Chandra Yadav, Srinivasa Murty Srinivasula

{"title":"Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2.","authors":"Nikhil Dev Narendradev, Rishith Ravindran, Parul Jain, Shikha Chaudhary, Anoop Kumar G Velikkakath, Abyasree Sudharman, Adithya Janardhanan, Tapas Chandra Nag, Subhash Chandra Yadav, Srinivasa Murty Srinivasula","doi":"10.1242/jcs.263830","DOIUrl":"10.1242/jcs.263830","url":null,"abstract":"Mitochondrial homeostasis is ensured through communication between diverse cellular organelles, including mitochondria, the endoplasmic reticulum (ER), lysosomes and endosomes. Although it is known that mitofusins regulate mitochondrial networks and ER contacts, their role in endosomal-mitochondrial interactions remains unclear. Previously, we have reported that vesicles positive for the endosomal ubiquitin ligase RFFL are associated with damaged mitochondria and prime the organelle for PRKN recruitment. Now, we establish that RFFL is a ubiquitin ligase for mitofusin 2 (MFN2). Using electron microscopy and confocal imaging analyses, we demonstrate that RFFL-knockout cells exhibit enlarged mitochondrial morphology. RFFL interacts at an endogenous level with MFN2 and contributes to its ubiquitylation upon mitochondrial damage. Recombinant RFFL interacts and ubiquitylates MFN2 protein in vitro. Furthermore, exogenous RFFL, in a ligase-dependent manner, specifically reduces the exogenous protein levels of both MFN1 and MFN2, but not that of DRP1, and also perturbs lipid homeostasis. Importantly, we show that the hyperfused mitochondria morphology reported with expression of pathogenic disease mutants of MFN2 (T206I and R364W) of Charcot-Marie-Tooth disease type 2A can be rescued by RFFL co-expression. The study unravels novel mechanisms involving endosomal ubiquitin ligases in mitochondrial networks.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182247","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

A cryo-electron microscopy structure of yeast Pex5 in complex with a cargo uncovers a novel binding interface. 酵母Pex5与货物复合物的低温电镜结构揭示了一个新的结合界面。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-15 Epub Date: 2025-06-26 DOI: 10.1242/jcs.263890

Lior Peer, Orly Dym, Nadav Elad, Asa Tirosh, Jossef Jacobovitch, Ehud Sivan, Mor Angel, Shira Albeck, Maya Schuldiner, Yoav Peleg, Einat Zalckvar

{"title":"A cryo-electron microscopy structure of yeast Pex5 in complex with a cargo uncovers a novel binding interface.","authors":"Lior Peer, Orly Dym, Nadav Elad, Asa Tirosh, Jossef Jacobovitch, Ehud Sivan, Mor Angel, Shira Albeck, Maya Schuldiner, Yoav Peleg, Einat Zalckvar","doi":"10.1242/jcs.263890","DOIUrl":"10.1242/jcs.263890","url":null,"abstract":"Proper protein targeting to organelles is crucial for maintaining eukaryotic cellular function and homeostasis. This necessity has driven the evolution of specific targeting signals on proteins and the targeting factors that recognize them. A prominent example is peroxisomal matrix proteins, most of which depend on the targeting factor Pex5 to localize and function correctly. Although most Pex5 cargoes contain a peroxisomal targeting signal type 1 (PTS1), they are not all targeted similarly. Some undergo priority targeting, facilitated either by stronger binding to specific subsets of PTS1 signals or by additional interaction interfaces. These observations highlight the extensive complexity of Pex5-mediated targeting. In this study, we reveal that the Saccharomyces cerevisiae (yeast) matrix protein Eci1 can reach peroxisomes and bind Pex5 in the absence of PTS1. By solving the structure of the yeast Pex5-Eci1 complex using cryo-electron microscopy, we identified additional binding interfaces. Our findings provide new insights into the versatile interactions between Pex5 and its cargo, Eci1. More broadly, this work highlights the intricate, dynamic nature of the interactions between cargo factors and their cargoes to meet the complex environment within eukaryotic cells.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078310","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

Intra-Golgi Golgin PpSgm1 and GRIP domain Golgin PpImh1 synergistically mediate Golgi cisternal stacking. 高尔基内Golgin PpSgm1和GRIP结构域Golgin PpImh1协同介导高尔基池堆积。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-01 Epub Date: 2025-06-05 DOI: 10.1242/jcs.263612

Roma Dahara, Dibyendu Bhattacharyya

{"title":"Intra-Golgi Golgin PpSgm1 and GRIP domain Golgin PpImh1 synergistically mediate Golgi cisternal stacking.","authors":"Roma Dahara, Dibyendu Bhattacharyya","doi":"10.1242/jcs.263612","DOIUrl":"10.1242/jcs.263612","url":null,"abstract":"Regulation of the distinctive stacked Golgi morphology remains an unresolved subject. Using the budding yeast Pichia pastoris, we have previously documented the role of GRIP domain Golgin P. pastoris (Pp)Imh1 in cisternal stacking, regulated by the Arl3-Arl1 GTPase cascade switch. Expanding our work with the present study, we demonstrate the participation of PpSgm1, another conserved Golgin, in this stacking process alongside PpImh1. Null mutation of P. pastoris SGM1 caused partial unstacking of the late cisternae from the Golgi stack, implicating its role in cisternal stacking. When we overexpressed PpImh1 or PpSgm1 independently, each failed to restore stacking in the absence of the other, suggesting neither of them is sufficient for cisternal stacking alone. On the other hand, a double knockout of PpIMH1 and PpSGM1 led to a dramatic phenotype, causing complete separation of the late cisternae from the Golgi stack and significantly increasing TGN peeling, as seen in electron microscopy and live-cell imaging. Our results suggest a synergistic collaboration of PpImh1 and PpSgm1 in cisternal stacking, with implications for a conserved mechanism across species.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020557","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

Glutamine modulates stress granule formation in cancer cells through core RNA-binding proteins. 谷氨酰胺通过核心rna结合蛋白调节癌细胞中的应激颗粒形成。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1242/jcs.263679

Gabriel P Faber, Gilad Gross, Oz Mualem, Matan Y Avivi, Hiba Waldman Ben-Asher, Orly Yaron, Noa Kinor, Orit Shefi, Rakefet Ben-Yishay, Dana Ishay-Ronen, Yaron Shav-Tal

{"title":"Glutamine modulates stress granule formation in cancer cells through core RNA-binding proteins.","authors":"Gabriel P Faber, Gilad Gross, Oz Mualem, Matan Y Avivi, Hiba Waldman Ben-Asher, Orly Yaron, Noa Kinor, Orit Shefi, Rakefet Ben-Yishay, Dana Ishay-Ronen, Yaron Shav-Tal","doi":"10.1242/jcs.263679","DOIUrl":"10.1242/jcs.263679","url":null,"abstract":"Cytoplasmic stress granules (SGs) induced by various stresses have been linked to cancer and other disorders. Which active energy pathways are required for SG formation remains unclear. We used nutrient deprivation to show that glutamine is the sole amino acid source governing whether cancer cells form SGs. Metabolic profiling revealed the essential functions of glutamine and glucose in SG formation under limiting metabolic conditions. Providing glutamine during metabolic stress restored ATP levels in cancer cells and revived many essential gene expression patterns. MYC, a known regulator of the shift between glucose and glutamine metabolism, showed increased expression as cells moved to glutamine uptake. Inhibition of MYC prevented SG formation even with glutamine present and increased cell death after arsenite exposure. The RNA-binding proteins G3BP1 and G3BP2 (collectively G3BP1/2) were required for glutamine utilization, with G3BP1/2-knockout cells displaying a heavier reliance on glucose, yielding reduced cell survival and an inability to properly utilize glutamine. Altogether, we show that cancer cells require glutamine for SG formation under nutrient deprivation, and its absence reduces cell survival, lowering ATP levels below an energy threshold required for SG formation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078318","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

AID-2×RBD27, an auxin-inducible degron-based Rab27 trapper that reversibly inhibits the function of Rab27A in melanocytes. AID-2×RBD27，一种生长素诱导的基于降解的Rab27诱捕剂，可逆地抑制黑素细胞中Rab27A的功能。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-01 Epub Date: 2025-06-09 DOI: 10.1242/jcs.263878

Akira Sugawara, Yuto Maruta, Mitsunori Fukuda

{"title":"AID-2×RBD27, an auxin-inducible degron-based Rab27 trapper that reversibly inhibits the function of Rab27A in melanocytes.","authors":"Akira Sugawara, Yuto Maruta, Mitsunori Fukuda","doi":"10.1242/jcs.263878","DOIUrl":"10.1242/jcs.263878","url":null,"abstract":"Small GTPase Rabs are evolutionarily conserved regulators of intracellular membrane traffic and regulate multiple steps in membrane trafficking. Although various approaches have been used to identify the function(s) of individual Rabs, no simple tool that reversibly inhibits the function of Rab has ever been reported. Here, we developed a novel tool, named AID-2×RBD27 (auxin-inducible degron-tagged tandem Rab27-binding domain), that reversibly inhibits the function of Rab27 and then evaluated its usefulness by using Rab27A-mediated melanosome transport as a model. We showed that expression and degradation of AID-2×RBD27 in melanocytes caused reversible changes in melanosome distribution between perinuclear melanosome aggregation and peripheral melanosome dispersion. By performing 3D live-cell imaging in combination, we found that two types of anterograde melanosome transport are involved in peripheral melanosome dispersion, i.e. fast, long-range melanosome transport in the microtubule-enriched inner cellular region, especially in the dendrite, and slow, intermittent melanosome transport along the cortical actin filaments. Our new concept of an auxin-inducible degron-Rab-binding domain system would apply to all other Rabs as a means of investigating various Rab-mediated membrane trafficking events by reversibly inhibiting them.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968016","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

LCN2 promotes focal adhesion formation and invasion by stimulating c-Src activation. LCN2通过刺激Src激活促进局灶黏附形成和侵袭。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-01 Epub Date: 2025-06-05 DOI: 10.1242/jcs.263663

Bhagya Shree Choudhary, Nazia Chaudhary, Bushra K Khan, Aditi Vijan, Dibita Mandal, Leena Pilankar, Shubham Gawand, Prerana Uttankar, Megha Sharma, Anusha Shivashankar, Rinki Doloi, Neha Joshi, Manjula Das, Sorab N Dalal

{"title":"LCN2 promotes focal adhesion formation and invasion by stimulating c-Src activation.","authors":"Bhagya Shree Choudhary, Nazia Chaudhary, Bushra K Khan, Aditi Vijan, Dibita Mandal, Leena Pilankar, Shubham Gawand, Prerana Uttankar, Megha Sharma, Anusha Shivashankar, Rinki Doloi, Neha Joshi, Manjula Das, Sorab N Dalal","doi":"10.1242/jcs.263663","DOIUrl":"10.1242/jcs.263663","url":null,"abstract":"Previous work has demonstrated that lipocalin2 (LCN2) expression promotes invasion and migration in multiple tumor types. The mechanisms by which LCN2 promotes invasion and migration remain unclear. Previous work from our laboratory demonstrated that LCN2 promotes actin filament formation by inhibiting actin glutathionylation. In this study, we demonstrate that, in addition to inhibiting actin glutathionylation, LCN2 stimulates invasion by promoting the formation of focal adhesions, which is independent of the ability of LCN2 to bind iron (Fe3+). We showed that LCN2 promotes focal adhesion formation by promoting the activation of c-Src (also known as SRC) by stimulating expression of the transcription factor ETS1. ETS1, in turn, upregulates expression of the protein phosphatase PTP1B, resulting in the auto-activation of c-Src and increased paxillin phosphorylation, leading to focal adhesion formation. These results demonstrate that LCN2 has iron-dependent and -independent functions in promoting invasion and highlight the multiple mechanisms by which LCN2 promotes invasion, suggesting that c-Src inhibitors could be used to treat invasive colorectal cancer.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018778","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

Focus on numbers - characterizing protein accumulation at DNA double-strand breaks. 关注数字：DNA双链断裂时蛋白质积累的特征。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1242/jcs.263483

Graziana Modica, Joannie Roy, Antoine G Godin, Hugo Wurtele, Santiago Costantino

{"title":"Focus on numbers - characterizing protein accumulation at DNA double-strand breaks.","authors":"Graziana Modica, Joannie Roy, Antoine G Godin, Hugo Wurtele, Santiago Costantino","doi":"10.1242/jcs.263483","DOIUrl":"10.1242/jcs.263483","url":null,"abstract":"Unrepaired DNA double-strand breaks can lead to cell death or genomic rearrangements. The DNA damage response (DDR) is a complex signaling cascade in which a plethora of factors act to finely tune repair pathway choice. Several DDR proteins have been shown to accumulate at sites of DNA lesions in characteristic dot-like structures known as DNA repair foci. Changes in foci brightness, commonly expressed in arbitrary intensity units, are often used as readout for DNA repair dynamics. However, due in part to technical challenges, the stoichiometry, absolute number of proteins recruited to DDR foci, and their impact on the resolution of the break remain incompletely characterized. Here, we combine spatial intensity distribution analysis (SpIDA) and a custom foci detection algorithm into an easy-to-use pipeline that, starting from confocal images, allows quantitative description of protein accumulation in DNA repair foci. Moreover, by quantifying foci based on their molecular count, SpIDA overcomes the limitations of ambiguous intensity units, enabling stoichiometric quantification between repair factors and providing a unifying means for experimental comparisons.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995007","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

Hypothesis that ancestral eukaryotes sexually proliferated without kinetochores or mitosis. 假设祖先真核生物有性繁殖，没有着丝点或有丝分裂。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-01 Epub Date: 2025-06-10 DOI: 10.1242/jcs.263843

Bungo Akiyoshi

{"title":"Hypothesis that ancestral eukaryotes sexually proliferated without kinetochores or mitosis.","authors":"Bungo Akiyoshi","doi":"10.1242/jcs.263843","DOIUrl":"10.1242/jcs.263843","url":null,"abstract":"Eukaryotes possess two different mechanisms to transmit genetic material - mitosis and meiosis. Because mitosis is universal in all present-day eukaryotes, it has been widely assumed, despite the absence of definitive evidence, that meiosis evolved from mitosis during eukaryogenesis. In both processes, chromosome movement depends on interactions between spindle microtubules and a macromolecular protein complex called the kinetochore that assembles onto centromere DNA. Spindle microtubules consist of α- and β-tubulin subunits, which are conserved in all studied eukaryotes. Similarly, canonical kinetochore components are found in almost all eukaryotes. However, an evolutionarily divergent group of organisms called kinetoplastids has a unique set of kinetochore proteins. It remains unclear why and when different types of kinetochores evolved. In this Hypothesis article, I propose that the last eukaryotic common ancestor (LECA) did not have a kinetochore and that these two kinetochore systems evolved independently - one in the ancestor of kinetoplastids and another in the ancestor of all other eukaryotes. Based on the notion that archaea and the LECA possessed cell fusion and genetic exchange machineries, I further propose that key aspects of meiosis evolved prior to mitosis, challenging the dogma that meiosis evolved from mitosis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258161","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

A minimal mathematical model for polarity establishment and centralspindlin-independent cytokinesis. 极性建立和不依赖中心纺锤体的细胞质分裂的最小数学模型。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-01 Epub Date: 2025-06-11 DOI: 10.1242/jcs.264093

Ondrej Maxian, Katrina M Longhini, Michael Glotzer

{"title":"A minimal mathematical model for polarity establishment and centralspindlin-independent cytokinesis.","authors":"Ondrej Maxian, Katrina M Longhini, Michael Glotzer","doi":"10.1242/jcs.264093","DOIUrl":"10.1242/jcs.264093","url":null,"abstract":"Cell polarization and cytokinesis are fundamental processes in organismal development. In the Caenorhabditis elegans model system, both processes are partially driven by local inhibition of contractility at the cell poles. This inhibition comes from Aurora A kinase (AIR-1), which is activated on centrosomes and diffuses to the cortex, where it inhibits the guanine nucleotide exchange factor (GEF) ECT-2, attenuating RHO-1 activation and actomyosin-based contractility. Although these biochemical processes have been characterized experimentally, a quantitative understanding of how this circuit drives cortical dynamics in polarization and cytokinesis is still lacking. Here, we constructed a mathematical model to test whether a minimal set of well-characterized, essential elements are necessary and sufficient to explain the spatiotemporal dynamics of AIR-1, ECT-2 and myosin during polarization and cytokinesis of C. elegans. We show that robust establishment of polarity can be obtained in response to a weak AIR-1 signal and demonstrate the relevance of rapid ECT-2 exchange and persistent AIR-1 cues during polarization. The model, tuned for polarization, can also predict ECT-2 accumulation during cytokinesis, suggesting a quantitative similarity between the two processes.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007467","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