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PKC? interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels.


ABSTRACT: PKC? is essential for the establishment of epithelial polarity and the normal assembly of tight junctions. We find that PKC? knockdown does not compromise the steady-state distribution of most tight junction proteins but results in increased transepithelial resistance (TER) and decreased paracellular permeability. Analysis of the levels of tight junction components demonstrates that claudin-2 protein levels are decreased. However, other tight junction proteins, such as claudin-1, ZO-1, and occludin, are unchanged. Incubation with an aPKC pseudosubstrate recapitulates the phenotype of PKC? knockdown, including increased TER and decreased levels of claudin-2. In addition, overexpression of PKC? results in increased claudin-2 levels. ELISA and coimmunoprecipitation show that the TGN/endosomal small GTPase Rab14 and PKC? interact directly. Immunolabeling shows that PKC? and Rab14 colocalize in both intracellular puncta and at the plasma membrane and that Rab14 expression is required for normal PKC? distribution in cysts in 3D culture. We showed previously that knockdown of Rab14 results in increased TER and decreased claudin-2. Our results suggest that Rab14 and aPKC interact to regulate trafficking of claudin-2 out of the lysosome-directed pathway.

SUBMITTER: Lu R 

PROVIDER: S-EPMC4395131 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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PKCι interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels.

Lu Ruifeng R   Dalgalan Dogukan D   Mandell Edward K EK   Parker Sara S SS   Ghosh Sourav S   Wilson Jean M JM  

Molecular biology of the cell 20150218 8


PKCι is essential for the establishment of epithelial polarity and the normal assembly of tight junctions. We find that PKCι knockdown does not compromise the steady-state distribution of most tight junction proteins but results in increased transepithelial resistance (TER) and decreased paracellular permeability. Analysis of the levels of tight junction components demonstrates that claudin-2 protein levels are decreased. However, other tight junction proteins, such as claudin-1, ZO-1, and occlu  ...[more]

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