FSGS3/CD2AP is a barbed-end capping protein that stabilizes actin and strengthens adherens junctions

Research output: Contribution to journalArticle

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 barbedend 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.

Original languageEnglish (US)
Pages (from-to)815-833
Number of pages19
JournalJournal of Cell Biology
Volume203
Issue number5
DOIs
StatePublished - Dec 9 2013

ASJC Scopus subject areas

  • Cell Biology

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