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Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3

Sorting nexin 27 (SNX27) contains a PDZ domain that is phylogenetically related to the PDZ domains of the NHERF proteins. Studies on nonepithelial cells have shown that this protein is located in endosomes, where it regulates trafficking of cargo proteins in a PDZ domain–dependent manner. However, t...

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Autores principales: Singh, Varsha, Yang, Jianbo, Cha, Boyoung, Chen, Tiane-e, Sarker, Rafiquel, Yin, Jianyi, Avula, Leela Rani, Tse, Ming, Donowitz, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472014/
https://www.ncbi.nlm.nih.gov/pubmed/25851603
http://dx.doi.org/10.1091/mbc.E14-12-1597
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author Singh, Varsha
Yang, Jianbo
Cha, Boyoung
Chen, Tiane-e
Sarker, Rafiquel
Yin, Jianyi
Avula, Leela Rani
Tse, Ming
Donowitz, Mark
author_facet Singh, Varsha
Yang, Jianbo
Cha, Boyoung
Chen, Tiane-e
Sarker, Rafiquel
Yin, Jianyi
Avula, Leela Rani
Tse, Ming
Donowitz, Mark
author_sort Singh, Varsha
collection PubMed
description Sorting nexin 27 (SNX27) contains a PDZ domain that is phylogenetically related to the PDZ domains of the NHERF proteins. Studies on nonepithelial cells have shown that this protein is located in endosomes, where it regulates trafficking of cargo proteins in a PDZ domain–dependent manner. However, the role of SNX27 in trafficking of cargo proteins in epithelial cells has not been adequately explored. Here we show that SNX27 directly interacts with NHE3 (C-terminus) primarily through the SNX27 PDZ domain. A combination of knockdown and reconstitution experiments with wild type and a PDZ domain mutant (GYGF → GAGA) of SNX27 demonstrate that the PDZ domain of SNX27 is required to maintain basal NHE3 activity and surface expression of NHE3 in polarized epithelial cells. Biotinylation-based recycling and degradation studies in intestinal epithelial cells show that SNX27 is required for the exocytosis (not endocytosis) of NHE3 from early endosome to plasma membrane. SNX27 is also required to regulate the retention of NHE3 on the plasma membrane. The findings of the present study extend our understanding of PDZ-mediated recycling of cargo proteins from endosome to plasma membrane in epithelial cells.
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spelling pubmed-44720142015-08-16 Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3 Singh, Varsha Yang, Jianbo Cha, Boyoung Chen, Tiane-e Sarker, Rafiquel Yin, Jianyi Avula, Leela Rani Tse, Ming Donowitz, Mark Mol Biol Cell Articles Sorting nexin 27 (SNX27) contains a PDZ domain that is phylogenetically related to the PDZ domains of the NHERF proteins. Studies on nonepithelial cells have shown that this protein is located in endosomes, where it regulates trafficking of cargo proteins in a PDZ domain–dependent manner. However, the role of SNX27 in trafficking of cargo proteins in epithelial cells has not been adequately explored. Here we show that SNX27 directly interacts with NHE3 (C-terminus) primarily through the SNX27 PDZ domain. A combination of knockdown and reconstitution experiments with wild type and a PDZ domain mutant (GYGF → GAGA) of SNX27 demonstrate that the PDZ domain of SNX27 is required to maintain basal NHE3 activity and surface expression of NHE3 in polarized epithelial cells. Biotinylation-based recycling and degradation studies in intestinal epithelial cells show that SNX27 is required for the exocytosis (not endocytosis) of NHE3 from early endosome to plasma membrane. SNX27 is also required to regulate the retention of NHE3 on the plasma membrane. The findings of the present study extend our understanding of PDZ-mediated recycling of cargo proteins from endosome to plasma membrane in epithelial cells. The American Society for Cell Biology 2015-06-01 /pmc/articles/PMC4472014/ /pubmed/25851603 http://dx.doi.org/10.1091/mbc.E14-12-1597 Text en © 2015 Singh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Singh, Varsha
Yang, Jianbo
Cha, Boyoung
Chen, Tiane-e
Sarker, Rafiquel
Yin, Jianyi
Avula, Leela Rani
Tse, Ming
Donowitz, Mark
Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3
title Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3
title_full Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3
title_fullStr Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3
title_full_unstemmed Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3
title_short Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3
title_sort sorting nexin 27 regulates basal and stimulated brush border trafficking of nhe3
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472014/
https://www.ncbi.nlm.nih.gov/pubmed/25851603
http://dx.doi.org/10.1091/mbc.E14-12-1597
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