Cholera toxin inhibits SNX27-retromer-mediated delivery of cargo proteins to the plasma membrane.

Journal of Cell Science
Varsha SinghMark Donowitz

Abstract

Cholera toxin (CT) causes severe diarrhea by increasing intracellular cAMP leading to a PKA-dependent increase in Cl- secretion through CFTR and decreased Na+ absorption through inhibition of Na+/H+ exchanger 3 (NHE3; also known as SLC9A3). The mechanism(s) by which CT inhibits NHE3 is partially understood, although no drug therapy has been successful at reversing this inhibition. We now describe that CT phosphorylates an amino acid in the PDZ domain of SNX27, which inhibits SNX27-mediated trafficking of NHE3 from the early endosomes to the plasma membrane (PM), and contributes to reduced basal NHE3 activity through a mechanism that involves reduced PM expression and reduced endocytic recycling. Importantly, mutagenesis studies (Ser to Asp) showed that the effect of this phosphorylation of SNX27 phenocopies the effects seen upon loss of SNX27 function, affecting PM trafficking of cargo proteins that bind SNX27-retromer. Additionally, CT destabilizes retromer function by decreasing the amount of core retromer proteins. These effects of CT can be partially rescued by enhancing retromer stability by using 'pharmacological chaperones'. Moreover, pharmacological chaperones can be used to increase basal and cholera toxin-inhibited NH...Continue Reading

References

Aug 26, 1998·Pflügers Archiv : European journal of physiology·J R SchwarkM Hropot
Feb 10, 1999·The American Journal of Physiology·M IkumaV M Rajendran
Jan 5, 2002·Physiological Reviews·Karl Kunzelmann, Marcus Mall
Jan 24, 2004·Lancet·David A SackA K Siddique
Apr 14, 2004·The Journal of Cell Biology·Cecilia N ArighiJuan S Bonifacino
Jun 19, 2004·Molecular Membrane Biology·Lolke De Haan, Timothy R Hirst
Jul 13, 2004·Nature Cell Biology·Marcel VergésKeith E Mostov
Feb 8, 2005·Trends in Cell Biology·Matthew N J Seaman
Nov 30, 2005·Annals of Neurology·Scott A SmallTae-Wan Kim
May 2, 2006·The Journal of Biological Chemistry·Rakhilya MurtazinaXuhang Li
Feb 20, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Mark W MuschEugene B Chang
Aug 11, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sandeep B SubramanyaHenry J Binder
Dec 28, 2007·Developmental Cell·Pei-Tzu YangHendrik C Korswagen
Apr 19, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Misa MizumoriYasutada Akiba
Apr 21, 2009·Nature Methods·Jacek R WiśniewskiMatthias Mann
Oct 17, 2009·Journal of Biology·Dagmar Ringe, Gregory A Petsko
Nov 21, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Mark W MuschEugene B Chang
Aug 25, 2010·The Journal of Cell Biology·Benjamin E L LaufferMark von Zastrow
Jul 19, 2011·American Journal of Human Genetics·Alexander ZimprichTim M Strom
Jun 8, 2012·Nature Communications·Alicia LundbyJesper V Olsen
Nov 29, 2012·Journal of Proteome Research·Houjiang ZhouShabaz Mohammed
Jun 4, 2013·Nature Medicine·Johanna F DekkersJeffrey M Beekman
Feb 5, 2014·Cold Spring Harbor Perspectives in Biology·Christopher Burd, Peter J Cullen
Apr 11, 2014·Experimental Biology and Medicine·Jennifer Foulke-AbelMark Donowitz
Apr 22, 2014·Nature Chemical Biology·Vincent J MecozziScott A Small
Aug 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Matthew GallonPeter J Cullen
Jan 22, 2015·The Journal of Biological Chemistry·Nikoleta G TsvetanovaMark von Zastrow
Apr 9, 2015·Molecular Biology of the Cell·Varsha SinghMark Donowitz
Nov 6, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tzer-Bin LinHsien-Yu Peng

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Citations

Mar 17, 2019·Clinical Science·Jian YangChunyu Zeng
Oct 24, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yiran Han, C Chris Yun
Dec 11, 2020·Biochemical Society Transactions·Ewan MacDonaldTobias Zech
Dec 31, 2020·Proceedings of the National Academy of Sciences of the United States of America·Zhike FengPeter D Nagy
Oct 23, 2020·Journal of Cellular Physiology·Lu YangJing Zhong
Apr 25, 2021·Science Advances·Sicong WangKenichiro Taniguchi
Nov 26, 2021·Cellular and Molecular Gastroenterology and Hepatology·Kayte A JenkinC Chris Yun

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