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First published online 12 February 2008
doi: 10.1242/jcs.016246

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Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells

¹ Department of Cell Biology and Anatomy
² Department of Pediatrics, University of Miami Miller School of Medicine, RMSB 4090–R124, 1600 NW 10th Avenue, Miami, FL 33135, USA

^* Author for correspondence (e-mail: psalas{at}med.miami.edu)

Accepted 5 December 2007

Atypical protein kinase iota (PKC) is a key organizer of the apical domain in epithelial cells. Ezrin is a cytosolic protein that, upon activation by phosphorylation of T567, is localized under the apical membrane where it connects actin filaments to membrane proteins and recruits protein kinase A (PKA). To identify the kinase that phosphorylates ezrin T567 in simple epithelia, we analyzed the expression of active PKC and the appearance of T567-P during enterocyte differentiation in vivo. PKC phosphorylated ezrin on T567 in vitro, and in Sf9 cells that do not activate human ezrin. In CACO-2 human intestinal cells in culture, PKC co-immunoprecipitated with ezrin and was knocked down by shRNA expression. The resulting phenotype showed a modest decrease in total ezrin, but a steep decrease in T567 phosphorylation. The PKC-depleted cells showed fewer and shorter microvilli and redistribution of the PKA regulatory subunit. Expression of a dominant-negative form of PKC also decreased T567-P signal, and expression of a constitutively active PKC mutant showed depolarized distribution of T567-P. We conclude that, although other molecular mechanisms contribute to ezrin activation, apically localized phosphorylation by PKC is essential for the activation and normal distribution of ezrin at the early stages of intestinal epithelial cell differentiation.

Key words: ERM proteins, Apical domain, Brush border, Epithelial polarity

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