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

is essential for the establishment of epithelial polarity and the normal assembly of tight junctions. We find that duanyu1531ι 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 pseudosubstrate recapitulates the phenotype of duanyu1531ι knockdown, including increased TER and decreased levels of claudin-2. In addition, overexpression of duanyu1531ι results in increased claudin-2 levels. ELISA and coimmunoprecipitation show that the TGN/endosomal small GTPase Rab14 and duanyu1531ι interact directly. Immunolabeling shows that duanyu1531ι and Rab14 colocalize in both intracellular puncta and at the plasma membrane and that Rab14 expression is required for normal duanyu1531ι 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 aduanyu1531 interact to regulate trafficking of claudin-2 out of the lysosome-directed pathway.

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