title: Sorting nexin 27 (SNX27) associates with zonula occludens-2 (ZO-2) and modulates the epithelial tight junction.
abstract: Proteins of the SNX (sorting nexin) superfamily are characterized by the presence of a PX (Phox homology) domain and associate with PtdIns3P (phosphatidylinositol-3-monophosphate)-rich regions of the endosomal system. SNX27 is the only sorting nexin that contains a PDZ domain. In the present study, we used a proteomic approach to identify a novel interaction between SNX27 and ZO-2 [zonula occludens-2; also known as TJP2 (tight junction protein 2)], 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 extracellular Ca2+, ZO-2 transiently localized to SNX27-positive early endosomes. Depletion of SNX27 in mpkCCD (mouse primary kidney cortical collecting duct) 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. The findings of the present study 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.
authors.affiliation: *Cell Biology and Physiology Center, National Institutes of Health, Bethesda, MD 20982, U.S.A.
authors.forename: Seth P
authors.initials: SP
authors.lastname: Zimmerman
authors.forename: Christina L
authors.initials: CL
authors.lastname: Hueschen
authors.forename: Daniela
authors.initials: D
authors.lastname: Malide
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Milgram
authors.forename: Martin P
authors.initials: MP
authors.lastname: Playford
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D061251:Primary Cell Culture; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D058305:Sorting Nexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D062827:Zonula Occludens-2 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C500393:Snx27 protein, mouse; D058305:Sorting Nexins; C569043:Tjp1 protein, mouse; C569047:Tjp2 protein, mouse; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein