Sorting Nexin 27 (SNX27) associates with Zona Occludens-2 (ZO-2) and modulates the epithelial tight junction

Proteins of the sorting nexin (SNX) superfamily are characterized by the presence of a phox-homology (PX) domain and associate with phosphatidylinositol-3-monophosphate (PtdIns3P) rich regions of the endosomal system. SNX27 is the only sorting nexin that contains a PDZ domain. Here, we used a proteomic approach to identify a novel interaction between SNX27 and zona occludens-2 (ZO-2, TJP2), a component of the epithelial tight junction. The SNX27-ZO-2 interaction requires the PDZ domain of SNX27 and the C-terminal PDZ-binding motif of ZO-2. When tight junctions were perturbed by chelation of intracellular Ca2+, ZO-2 transiently localized to SNX27-positive early endosomes. Depletion of SNX27 in mpkCCD cell monolayers resulted in a decrease in the rate of ZO-2, but not ZO-1 mobility at cell-cell contact regions after photobleaching and an increase in junctional permeability to large solutes. Our findings identify an important new SNX27 binding partner and suggest a role for endocytic pathways in the intracellular trafficking of ZO-2 and possibly other tight junction proteins. Our results also indicate a role for SNX27-ZO-2 interactions in tight junction maintenance and function.

Source: BJ Cell - July 4, 2013 Category: Biochemistry Authors: S Paul Zimmerman, C Lynn Hueschen, D Malide, S Lynn Milgram, M Peter Playford Tags: BJ Cell Source Type: research