| Autor: |
Walker C; Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States., Chandrasekaran A; Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, United States., Mansour D; Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, United States., Graham K; Cell and Molecular Biology, The University of Texas at Austin, Austin, TX, United States., Torres A; Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States., Wang L; Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Lafer EM; Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States., Rangamani P; Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, United States., Stachowiak JC; Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States.; Chemical Engineering, The University of Texas at Austin, Austin, TX, United States. |
| Abstrakt: |
Liquid-like protein condensates perform diverse physiological functions. Previous work showed that VASP, a processive actin polymerase, forms condensates that polymerize and bundle actin. To minimize their curvature, filaments accumulated at the inner condensate surface, ultimately deforming the condensate into a rod-like shape, filled with a bundle of parallel filaments. Here we show that this behavior does not require proteins with specific polymerase activity. Specifically, we found that condensates composed of Lamellipodin, a protein that binds actin but is not an actin polymerase, were also capable of polymerizing and bundling actin filaments. To probe the minimum requirements for condensate-mediated actin bundling, we developed an agent-based computational model. Guided by its predictions, we hypothesized that any condensate-forming protein that binds actin could bundle filaments through multivalent crosslinking. To test this idea, we added an actin-binding motif to Eps15, a condensate-forming protein that does not normally bind actin. The resulting chimera formed condensates that drove efficient actin polymerization and bundling. Collectively, these findings broaden the family of proteins that could organize cytoskeletal filaments to include any actin-binding protein that participates in protein condensation. |
