PTEN dephosphorylates Abi1 to promote epithelial morphogenesis.

The Journal of Cell Biology
Yanmei QiShaohua Li

Abstract

The tumor suppressor PTEN is essential for early development. Its lipid phosphatase activity converts PIP3 to PIP2 and antagonizes the PI3K-Akt pathway. In this study, we demonstrate that PTEN's protein phosphatase activity is required for epiblast epithelial differentiation and polarization. This is accomplished by reconstitution of PTEN-null embryoid bodies with PTEN mutants that lack only PTEN's lipid phosphatase activity or both PTEN's lipid and protein phosphatase activities. Phosphotyrosine antibody immunoprecipitation and mass spectrometry were used to identify Abi1, a core component of the WASP-family verprolin homologous protein (WAVE) regulatory complex (WRC), as a new PTEN substrate. We demonstrate that PTEN dephosphorylation of Abi1 at Y213 and S216 results in Abi1 degradation through the calpain pathway. This leads to down-regulation of the WRC and reorganization of the actin cytoskeleton. The latter is critical to the transformation of nonpolar pluripotent stem cells into the polarized epiblast epithelium. Our findings establish a link between PTEN and WAVE-Arp2/3-regulated actin cytoskeletal dynamics in epithelial morphogenesis.

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
immunoprecipitation
transfection
coimmunoprecipitation
pull-down
genotyping
fluorescence microscopy
FACS
PCR
protein assay
electrophoresis

Key Resources (RRID) Mentioned

AB_2265207
AB_2069843
AB_2216981
AB_2253290
AB_2631168
AB_1056051
AB_592744
AB_390148
AB_309655
AB_2167703

Software Mentioned

IP Lab
ImageJ
Affymetrix
IP
Proteome Discover
MAS
Global Proteome Machine

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