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Sorting Nexin 27 mediates PDZ‐directed trafficking of Zona‐Occludens (ZO)‐2 to the Tight Junction
Author(s) -
Hueschen Christina Lynn,
Zimmerman Seth Paul,
Milgram Sharon Lynn,
Playford Martin Peter
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.275.4
Subject(s) - sorting nexin , pdz domain , microbiology and biotechnology , tight junction , endocytic cycle , retromer , chemistry , endosome , claudin , intracellular , biology , endocytosis , biochemistry , cell
Proteins of the sorting nexin (SNX) superfamily are characterized by the presence of a phox‐homology (PX) domain. SNX27 is unique in being the only sorting nexin to contain a PDZ domain. 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+, we observed a transient co‐localization of ZO‐1 and ZO‐2 on SNX27‐positive early endosomes. Decreasing SNX27 expression in mpkCCD monolayers caused a decrease in the rate of ZO‐2 mobility, an enhancement of junctional permeability to large solutes, and an increase in the transepithelial resistance of monolayers. In addition to identifying an important new binding partner of SNX27, these findings suggest a role for endocytic pathways in the intracellular trafficking of ZO‐2 and possibly other tight junction proteins. Our results also indicate the involvement of the SNX27‐ZO‐2 interaction in tight junction maintenance and function.