Association of Rho-associated protein kinase 1 with E-cadherin complexes is mediated by p120-catenin.

Smith AL, Dohn MR, Brown MV, Reynolds AB
Mol Biol Cell. 2012 23 (1): 99-110

PMID: 22031287 · PMCID: PMC3248908 · DOI:10.1091/mbc.E11-06-0497

The dynamic functional linkage of cadherins with the underlying actin cytoskeleton is tightly regulated to achieve proper cell-cell adhesion. p120-catenin (p120) regulates both cadherin stability and actin dynamics, but the relationship between these two functions remains unclear. Using a novel proteomic approach called reversible cross-link immunoprecipitation, or ReCLIP, we previously identified a physical interaction between p120 and Rho-associated protein kinase 1 (ROCK1), a major effector of RhoA. In this paper, we show that a discrete fraction of cellular ROCK1 coimmunoprecipitates with p120 and precisely colocalizes to adherens junctions (AJs). Manipulation of AJs using a calcium-switch assay and cadherin-blocking antibodies indicates direct recruitment of ROCK1 to newly forming junctions. Importantly, we find that p120 links ROCK1 to the cadherin complex, as ROCK1 coimmunoprecipitates with wild-type but not p120-uncoupled E-cadherin. Moreover, depletion of ROCK1 using short-hairpin RNA results in dramatic mislocalization of the cadherin complex and junctional actin. These data are consistent with a model in which p120 dynamically regulates Rho-GTPase activity at the cadherin complex through transient interaction with several of its up- and downstream effectors, including ROCK1.

MeSH Terms (16)

Actins Cadherins Catenins Cell Line Gene Knockdown Techniques Guanine Nucleotide Exchange Factors Humans Intercellular Junctions Microscopy, Fluorescence Multiprotein Complexes Protein Binding Protein Interaction Mapping Protein Transport Repressor Proteins rho-Associated Kinases RNA Interference

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