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.
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Research Article|
September 13 2013
Sorting nexin 27 (SNX27) associates with zonula occludens-2 (ZO-2) and modulates the epithelial tight junction
Seth P. Zimmerman;
Seth P. Zimmerman
*Cell Biology and Physiology Center, National Institutes of Health, Bethesda, MD 20982, U.S.A.
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Christina L. Hueschen;
Christina L. Hueschen
*Cell Biology and Physiology Center, National Institutes of Health, Bethesda, MD 20982, U.S.A.
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Daniela Malide;
Daniela Malide
†NHLBI Light Microscopy Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20982, U.S.A.
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Sharon L. Milgram;
Sharon L. Milgram
*Cell Biology and Physiology Center, National Institutes of Health, Bethesda, MD 20982, U.S.A.
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Martin P. Playford
Martin P. Playford
1
*Cell Biology and Physiology Center, National Institutes of Health, Bethesda, MD 20982, U.S.A.
1To whom correspondence should be addressed (email playfordmp@nhlbi.nih.gov).
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Publisher: Portland Press Ltd
Received:
November 19 2012
Revision Received:
June 18 2013
Accepted:
July 04 2013
Accepted Manuscript online:
July 04 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 455 (1): 95–106.
Article history
Received:
November 19 2012
Revision Received:
June 18 2013
Accepted:
July 04 2013
Accepted Manuscript online:
July 04 2013
Citation
Seth P. Zimmerman, Christina L. Hueschen, Daniela Malide, Sharon L. Milgram, Martin P. Playford; Sorting nexin 27 (SNX27) associates with zonula occludens-2 (ZO-2) and modulates the epithelial tight junction. Biochem J 1 October 2013; 455 (1): 95–106. doi: https://doi.org/10.1042/BJ20121755
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