title: FSGS3/CD2AP is a barbed-end capping protein that stabilizes actin and strengthens adherens junctions.
abstract: By combining in vitro reconstitution biochemistry with a cross-linking approach, we have identified focal segmental glomerulosclerosis 3/CD2-associated protein (FSGS3/CD2AP) as a novel actin barbed-end capping protein responsible for actin stability at the adherens junction. FSGS3/CD2AP colocalizes with E-cadherin and α-actinin-4 at the apical junction in polarized Madin-Darby canine kidney (MDCK) cells. Knockdown of FSGS3/CD2AP compromised actin stability and decreased actin accumulation at the adherens junction. Using a novel apparatus to apply mechanical stress to cell-cell junctions, we showed that knockdown of FSGS3/CD2AP compromised adhesive strength, resulting in tearing between cells and disruption of barrier function. Our results reveal a novel function of FSGS3/CD2AP and a previously unrecognized role of barbed-end capping in junctional actin dynamics. Our study underscores the complexity of actin regulation at cell-cell contacts that involves actin activators, inhibitors, and stabilizers to control adhesive strength, epithelial behavior, and permeability barrier integrity.
authors: Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, IL 61820.
authors: Vivian W
authors: VW
authors: Tang
authors: William M
authors: WM
authors: Brieher
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D022005:Adherens Junctions / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D004285:Dogs; D055785:Gene Knockdown Techniques; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D058105:Polymerization; D017434:Protein Structure, Tertiary
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins