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Nat Cell Biol. 2011 Jul 24;13(8):934-43. doi: 10.1038/ncb2290.

N-WASP regulates the epithelial junctional actin cytoskeleton through a non-canonical post-nucleation pathway.

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1
Division of Molecular Cell Biology, Institute for Molecular Bioscience, School of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.

Abstract

N-WASP is a major cytoskeletal regulator that stimulates Arp2/3-mediated actin nucleation. Here, we identify a nucleation-independent pathway by which N-WASP regulates the cytoskeleton and junctional integrity at the epithelial zonula adherens. N-WASP is a junctional protein whose depletion decreased junctional F-actin content and organization. However, N-WASP (also known as WASL) RNAi did not affect junctional actin nucleation, dominantly mediated by Arp2/3. Furthermore, the junctional effect of N-WASP RNAi was rescued by an N-WASP mutant that cannot directly activate Arp2/3. Instead, N-WASP stabilized newly formed actin filaments and facilitated their incorporation into apical rings at the zonula adherens. A major physiological effect of N-WASP at the zonula adherens thus occurs through a non-canonical pathway that is distinct from its capacity to activate Arp2/3. Indeed, the junctional impact of N-WASP was mediated by the WIP-family protein, WIRE, which binds to the N-WASP WH1 domain. We conclude that N-WASP-WIRE serves as an integrator that couples actin nucleation with the subsequent steps of filament stabilization and organization necessary for zonula adherens integrity.

Comment in

PMID:
21785420
DOI:
10.1038/ncb2290
[Indexed for MEDLINE]

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