{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Phua DYZ"],"funding":["NHLBI NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["As the cytoskeleton sustains cell and tissue forces, it incurs physical damage that must be repaired to maintain mechanical homeostasis. The LIM-domain protein zyxin detects force-induced ruptures in actin-myosin stress fibers, coordinating downstream repair factors to restore stress fiber integrity through unclear mechanisms. Here, we reconstitute stress fiber repair with purified proteins, uncovering detailed links between zyxin's force-regulated binding interactions and cytoskeletal dynamics. In addition to binding individual tensed actin filaments (F-actin), zyxin's LIM domains form force-dependent assemblies that bridge broken filament fragments. Zyxin assemblies engage repair factors through multi-valent interactions, coordinating nucleation of new F-actin by VASP and its crosslinking into aligned bundles by ɑ-actinin. Through these combined activities, stress fiber repair initiates within the cores of micron-scale damage sites in cells, explaining how these F-actin depleted regions are rapidly restored. Thus, zyxin's force-dependent organization of actin repair machinery inherently operates at the network scale to maintain cytoskeletal integrity."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.05.17.594765"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11118565"],"repository":["biostudies-literature"],"pubmed_title":["Force-activated zyxin assemblies coordinate actin nucleation and crosslinking to orchestrate stress fiber repair."],"pmcid":["PMC11118565"],"funding_grant_id":["F31 HL165906","R01 GM146880"],"pubmed_authors":["Phua DYZ","Sun X","Alushin GM"],"additional_accession":[]},"is_claimable":false,"name":"Force-activated zyxin assemblies coordinate actin nucleation and crosslinking to orchestrate stress fiber repair.","description":"As the cytoskeleton sustains cell and tissue forces, it incurs physical damage that must be repaired to maintain mechanical homeostasis. The LIM-domain protein zyxin detects force-induced ruptures in actin-myosin stress fibers, coordinating downstream repair factors to restore stress fiber integrity through unclear mechanisms. Here, we reconstitute stress fiber repair with purified proteins, uncovering detailed links between zyxin's force-regulated binding interactions and cytoskeletal dynamics. In addition to binding individual tensed actin filaments (F-actin), zyxin's LIM domains form force-dependent assemblies that bridge broken filament fragments. Zyxin assemblies engage repair factors through multi-valent interactions, coordinating nucleation of new F-actin by VASP and its crosslinking into aligned bundles by ɑ-actinin. Through these combined activities, stress fiber repair initiates within the cores of micron-scale damage sites in cells, explaining how these F-actin depleted regions are rapidly restored. Thus, zyxin's force-dependent organization of actin repair machinery inherently operates at the network scale to maintain cytoskeletal integrity.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-07-09T12:23:09.347Z","creation":"2026-07-09T11:16:38.637Z"},"accession":"S-EPMC11118565","cross_references":{"pubmed":["38798419"],"doi":["10.1101/2024.05.17.594765"]}}