Analysis of the assembly, stabilization and maturation of multiphasic TAZ biomolecular condensates

Analysis of the assembly, stabilization and maturation of multiphasic TAZ biomolecular condensates | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Analysis of the assembly, stabilization and maturation of multiphasic TAZ biomolecular condensates Kunxin Luo, Keren Shapira, Qingwei Zhu, Eden Grig, Xiaomin Chen, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8866112/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Phase separation is an important mechanism ensuring efficient regulation and function in Hippo signaling. Particularly, phase separation of nuclear TAZ has been demonstrated to be essential for its activity. However, the mechanisms of TAZ condensate assembly and maturation are yet undefined. Here we explored these mechanisms using FRAP with two laser beam sizes complemented by microscopy and cell biology approaches. We show that TAZ condensates are multiphasic, with a more stable core and labile periphery. TAZ initially forms small nascent clusters, likely via self-nucleation through the CC domain. These gradually mature into larger condensates through interaction with additional proteins via the WW domain. The condensates are further stabilized/activated by interaction with transcription factors and complexes including TEAD4 and P-TEFb. Of note, the ability of TAZ to form mature condensates is essential for its activities in cellular morphogenesis and tumorigenesis. Our study presents detailed mechanistic analysis of TAZ phase separation, revealing a highly dynamic nature of TAZ condensate maturation and activation. Biological sciences/Cancer/Breast cancer Biological sciences/Cell biology/Nuclear organization Biological sciences/Biophysics/Intrinsically disordered proteins TAZ Hippo signaling 3D acini morphogenesis biomolecular condensates nascent clusters multiphasic condensates phase separation FRAP beam-size analysis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMovie1mCherryCycT1inliveHeLacells.mp4 mCherry-CycT1 in live HeLa cells SupplementaryMovie2GFPTAZrecruitsmCherryCycT1intonuclearcondensates.mp4 GFP-TAZ recruits mCherry-CycT1 into nuclear condensates Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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