https://fctsai.com/project/ProjectsSource Themes Academic (https://sourcethemes.com/academic/)en-us© 2020 Feng-Ching TsaiFri, 12 Jan 2024 00:00:00 +0000https://fctsai.com/images/icon_hu0b7a4cb9992c9ac0e91bd28ffd38dd00_9727_512x512_fill_lanczos_center_2.pnghttps://fctsai.com/project/https://fctsai.com/project/filopodia-project/Fri, 12 Jan 2024 00:00:00 +0000https://fctsai.com/project/filopodia-project/<p><strong>Scientific question</strong> Filopodia are actin-filled finger-like membrane protrusions that are important for cell function, including migration and exploration of the environment, but their formation and regulation mechanisms are not fully understood. Cell biology studies have shown that the curvature-sensing protein IRSp53 promotes filopodia formation by interacting with VASP, which enhances actin polymerization. However, the underlying molecular mechanism of IRSp53-driven filopodia formation remains elusive.</p> <p><strong>Our Contribution</strong> We have developed in vitro reconstitution assays to demonstrate the ability of the curvature-sensing protein IRSp53 to orchestrate local actin assembly on membranes, leading to the formation of membrane tubes. The in vitro assays use giant unilamellar vesicles (GUVs) as model membranes and purified IRSp53, VASP, actin and fascin. We demonstrated that IRSp53 clusters recruit VASP to assemble actin filaments on membranes, generating actin-filled protrusions that resemble filopodia. We found that IRSp53 is enriched and induces actin assembly only in highly dynamic membrane regions of nanotubes pulled from living cells.</p> <p><strong>Impact</strong> Our findings advance the understanding of a fundamental question in biophysics and cell biology: how cells initiate actin-driven protrusions, such as filopodia, at specific membrane locations. Our work supports a regulatory mechanism of IRSp53 for precise spatio-temporal control of filopodia initiation and stabilization.</p> <p><strong>Related publications</strong></p> <ul> <li> <p> <a href="https://fctsai.com/publication/tsai-2018-ezrin/">2018. Ezrin enrichment on curved membranes requires a specific conformation or interaction with a curvature-sensitive partner</a></p> </li> <li> <p> <a href="https://www.science.org/doi/10.1126/sciadv.abp8677" target="_blank" rel="noopener">2020. Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions</a></p> </li> </ul>https://fctsai.com/project/bar-project/Fri, 26 Jun 2020 00:00:00 +0000https://fctsai.com/project/bar-project/<p>BAR domain containing proteins have been well-recognized to be involved in numerous cellular processes, such as endocytosis and intracellular trafficking, where the cellular membranes undergo remarkable shape change. Due to their crescent shape, BAR domains have a high propensity to bind to curved membranes matching their intrinsic curvature, which contributes to their recruitment at highly curved membrane regions in cells. Also, BAR domains can deform membranes, which contributes to membrane reshaping in cells. Yet, a comprehensive mechanistic description of how BAR proteins sense and generate membrane curvature is missing. We aim to <strong>reveal the mechanisms underlying the membrane curvature sensing and deformation abilities of BAR proteins</strong> by using biophysical approaches, such as membrane nanotube pulling using optical tweezers, and bottom-up reconstitution systems composed of GUVs and purified BAR proteins.</p> <p><strong>Related publications</strong></p> <ul> <li> <a href="https://fctsai.com/publication/jarin-2019-ibar/">Unusual Organization of I-BAR Proteins on Tubular and Vesicular Membranes</a></li> <li> <a href="https://fctsai.com/publication/prevost-2017-jove/">Pulling membrane nanotubes from giant unilamellar vesicles</a></li> </ul>