{"title":"Phosphoproteomic Analysis of CARMIL1 Reveals Novel Regulatory Mechanisms and Upstream Kinases Involved in Actin Dynamics and Cell Migration","authors":"Akhila Sheela, Althaf Mahin, Samseera Ummar, Nazah Naurah Vattoth, Leona Dcunha, Athira Perunelly Gopalakrishnan, Rajesh Raju","doi":"10.1002/cm.70001","DOIUrl":"10.1002/cm.70001","url":null,"abstract":"<div>\u0000 \u0000 <p>Capping protein regulator and myosin 1 Linker 1 (CARMIL1) is a multifunctional regulator of actin polymerization, ruffle formation, and lamellipodia development, making it essential for cell spreading and migration. While its protein-level functions are perceived, phospho-signaling of highly phosphorylated CARMIL1 remains unexplored. This study investigates CARMIL1 phosphorylation and its regulatory mechanisms. Global phosphoproteome datasets captured the most frequently detected and differentially regulated CARMIL1 phosphosites under different conditions to be in the CARMIL_C domain (T916, S968, and S1067). A coregulation-based method was employed to identify interactors and upstream kinases that are coregulated with the phosphorylation sites. These sites exhibited a consistent co-occurrence pattern including both positive and negative coregulation. The phosphosites of complex interactors showed positive and negative coregulation and were involved in cell cycle regulation and cell growth. AKT1, PAK2, and MYLK were identified as potential upstream kinases for CARMIL at S968, while WNK1 was predicted as a potential upstream kinase for S1067, suggesting distinct regulatory mechanisms for these phosphorylation sites. Phosphorylation at CDK1 S146, MAP4K2 S238, MINK1 S641, and TNIK S678 was found coregulated high with CARMIL T916 in human brain cancer. Notably, most coregulated proteins were associated with regulation of the actin cytoskeleton pathway. Our results show that phosphorylation of CARMIL1 in the C-terminal domain highly influences actin cytoskeletal organization. It offers new insights on CARMIL1-mediated cellular functions, deepening our comprehension of its involvement in cytoskeletal dynamics.</p>\u0000 </div>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 3","pages":"151-164"},"PeriodicalIF":1.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-03-16Epub Date: 2026-02-23DOI: 10.1002/cm.70119
{"title":"Picture of the Month by Catarina Peneda","authors":"","doi":"10.1002/cm.70119","DOIUrl":"10.1002/cm.70119","url":null,"abstract":"","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-03-16Epub Date: 2026-02-23DOI: 10.1002/cm.70118
{"title":"Picture of the Month by Catarina Peneda","authors":"","doi":"10.1002/cm.70118","DOIUrl":"10.1002/cm.70118","url":null,"abstract":"","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-03-16Epub Date: 2025-06-16DOI: 10.1002/cm.22052
Catarina Peneda, Joana N. Bugalhao, Marco Antonio Dias Louro, Andreia Henriques-Soares, Monica Bettencourt-Dias
{"title":"LZTS2 Negatively Regulates Centrosomal CEP135 Levels and Microtubule Nucleation","authors":"Catarina Peneda, Joana N. Bugalhao, Marco Antonio Dias Louro, Andreia Henriques-Soares, Monica Bettencourt-Dias","doi":"10.1002/cm.22052","DOIUrl":"10.1002/cm.22052","url":null,"abstract":"<p>The microtubule cytoskeleton is a fundamental functional component of the cell. In vertebrate proliferating cells, centrosomes are the primary microtubule organizing center (MTOC), and their dysregulation has been linked to genomic instability and cancer. LZTS2, a known tumor suppressor, localizes to centrosomes and regulates microtubule severing. However, whether LZTS2 regulates centrosome structure and/or its function in microtubule organization or ciliation remains unknown. Here, we investigate the function of LZTS2 at the centrosome. Through fluorescence and electron microscopy assays, we observed that LZTS2 knockdown does not affect centriole biogenesis or structure, nor ciliation. Importantly, we show that LZTS2 depletion increases microtubule nucleation at the centrosome. Moreover, LZTS2 negatively regulates centrosomal levels of CEP135. Notably, depletion of LZTS2 can partially rescue the impaired centrosome microtubule nucleation caused by CEP135 knockdown. Taken together, our findings reveal a novel role for LZTS2 as a negative regulator of CEP135 and centrosomal microtubule nucleation, providing a potential mechanistic link to its tumor suppressor function.</p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 3","pages":"128-139"},"PeriodicalIF":1.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12993252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-03-16Epub Date: 2026-02-23DOI: 10.1002/cm.70117
{"title":"Picture of the Month by Catarina Peneda","authors":"","doi":"10.1002/cm.70117","DOIUrl":"10.1002/cm.70117","url":null,"abstract":"","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-02-13DOI: 10.1002/cm.70103
{"title":"Front Cover Image","authors":"","doi":"10.1002/cm.70103","DOIUrl":"https://doi.org/10.1002/cm.70103","url":null,"abstract":"<p>ON THE FRONT COVER: Cytoskeleton on Display: COS-7 cells with free tubulin extracted and stained for microtubules (total α-tubulin, green) and actin filaments (phalloidin, red), and nuclei (Hoechst, blue).</p><p>Credit: Sareen Fiaz, Benjamin Powers, and Jayne Aiken (Colorado State University).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146680419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-02-13DOI: 10.1002/cm.70106
{"title":"Back Cover Image","authors":"","doi":"10.1002/cm.70106","DOIUrl":"https://doi.org/10.1002/cm.70106","url":null,"abstract":"<p>ON THE BACK COVER: An expansion microscopy image of the ciliate Tetrahymena stained for total tubulin (green) and DNA (pink) in the ciliateTetrahymena.</p><p>Credit: Babette van Amen (Neurobiology and Biophysics Department, Utrecht University, The Netherlands).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146680447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-02-13DOI: 10.1002/cm.70104
{"title":"Inner Front Cover Image","authors":"","doi":"10.1002/cm.70104","DOIUrl":"https://doi.org/10.1002/cm.70104","url":null,"abstract":"<p>ON THE INNER FRONT COVER: Live-cell Airyscan confocal image of actin filaments in an open stoma of an Arabidopsis leaf expressing LifeAct–TdTomato (magenta).</p><p>Credit: Camila Goldy and Marie-Cécile Caillaud (Laboratoire Reproduction et Développement des Plantes (RDP), Université de Lyon, Lyon, France).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146680418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-02-13DOI: 10.1002/cm.70105
{"title":"Inner Back Cover Image","authors":"","doi":"10.1002/cm.70105","DOIUrl":"https://doi.org/10.1002/cm.70105","url":null,"abstract":"<p>ON THE INNER BACK COVER: Time-lapse fluorescent single-molecule speckle images of fish keratocyte loaded with DyLight550-actin.</p><p>Credit: Soichiro Tanaka (Tohoku University Graduate School of Life Sciences) and Sawako Yamashiro (Kyoto University Graduate School of Biostudies).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147268991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytoskeletonPub Date : 2026-02-04DOI: 10.1002/cm.70099
{"title":"Picture of the Month by Xuwei Chen","authors":"","doi":"10.1002/cm.70099","DOIUrl":"10.1002/cm.70099","url":null,"abstract":"","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"83 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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