Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism

Biochemical and Biophysical Research Communications
Sunil K SaxenaMitsunori Fukuda

Abstract

Liddle's syndrome (excessive absorption of sodium ions) and PHA-1 (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein-protein interaction in HT-29 cells. We hereby report that Rab27a-dependent inhibition is associated with the GTP/GDP status as constitutively active or GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP-locked inactive mutant T23N showed no effect. In order to further explore the molecular mechanism of this regulation, we performed competitive assays with two Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a putative priming factor for exocytosis). Both proteins eliminate negative modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was restricted to C-terminal C2A/C2B domains assigned for putative phospholipids-binding function while the Rab27a-binding SHD motif imparted higher inhibition. The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to strongly ...Continue Reading

References

Jun 3, 2000·Nature Genetics·G MénaschéG de Saint Basile
Sep 16, 2000·Current Opinion in Nephrology and Hypertension·D Rotin
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·M Zerial, H McBride
Mar 27, 2001·The Journal of Cell Biology·J C StinchcombeG M Griffiths
Jan 5, 2002·The Journal of Biological Chemistry·Taruho S KurodaKatsuhiko Mikoshiba
Feb 28, 2002·Molecular and Cellular Biology·Zhaohong YiTetsuro Izumi
Jun 8, 2002·Biochemical and Biophysical Research Communications·Taruho S KurodaKatsuhiko Mikoshiba
Jun 13, 2002·The Journal of Investigative Dermatology·Yanru ChenSeth J Orlow
Aug 15, 2002·The Journal of Biological Chemistry·Mitsunori FukudaTaruho S Kuroda
Dec 4, 2002·The Biochemical Journal·Kelly GormleyGiuseppe A Sagnella
Jan 18, 2003·Current Hypertension Reports·Edith Hummler
Nov 18, 2003·Molecular Biology of the Cell·Tanya TolmachovaMiguel C Seabra
Dec 31, 2003·The Journal of Biological Chemistry·Ryutaro ShirakawaHisanori Horiuchi
Jan 15, 2004·The Journal of Biological Chemistry·Mitsunori FukudaAkitsugu Yamamoto
Jan 28, 2004·Cell Structure and Function·Tetsuro IzumiSeiji Torii
Feb 24, 2004·Molecular Biology of the Cell·Clare E FutterMiguel C Seabra
Mar 19, 2004·Current Biology : CB·Benjamin Short, Francis A Barr
Mar 25, 2004·Journal of Cell Science·Akane ImaiMitsunori Fukuda
Apr 13, 2004·American Journal of Physiology. Renal Physiology·Soo Wan KimSøren Nielsen
Sep 21, 2004·Nature Structural & Molecular Biology·Guangyu ZhuXuejun C Zhang
Oct 7, 2004·Biochemical and Biophysical Research Communications·Keiichi GoishiTakuya Sasaki
Oct 20, 2004·Current Opinion in Plant Biology·Arthur J MolendijkKlaus Palme
Nov 19, 2004·Molecular Biology of the Cell·Maaike NeeftPeter van der Sluijs
Feb 4, 2005·The Journal of Clinical Investigation·Toru Aizawa, Mitsuhisa Komatsu
Feb 4, 2005·The Journal of Clinical Investigation·Kazuo KasaiTetsuro Izumi
Apr 23, 2005·Toxicology and Applied Pharmacology·Nazzareno BallatoriRosemarie Marchan
Sep 10, 2005·Endocrinology·Peter M Snyder
Oct 21, 2005·Biochemical and Biophysical Research Communications·Sunil SaxenaSimarna Kaur
Jan 4, 2006·Biochemical and Biophysical Research Communications·Sunil K SaxenaConstantine George
Feb 17, 2006·Molecular Biology of the Cell·Takashi Tsuboi, Mitsunori Fukuda
Mar 24, 2006·Biochemical and Biophysical Research Communications·Mitsunori Fukuda

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Citations

Mar 12, 2009·Pflügers Archiv : European journal of physiology·Johannes Loffing, Christoph Korbmacher
Dec 2, 2011·American Journal of Physiology. Renal Physiology·Michael B ButterworthJohn P Johnson
May 30, 2008·American Journal of Physiology. Renal Physiology·Michael B ButterworthJohn P Johnson
Mar 13, 2012·Experimental Cell Research·Ossama B Kashlan, Thomas R Kleyman
Nov 7, 2006·Biochemical and Biophysical Research Communications·Sunil K Saxena, Simarna Kaur
Mar 30, 2010·Biochimica Et Biophysica Acta·Michael B Butterworth
Mar 30, 2010·Biochimica Et Biophysica Acta·Sylvie CayouetteGuylain Boulay
Oct 26, 2007·Experimental Biology and Medicine·Oleh PochynyukAlexander Staruschenko
Aug 30, 2008·Journal of the American Society of Nephrology : JASN·Vivek Bhalla, Kenneth R Hallows
Jun 24, 2020·Cells·Tilman GrossWiebke Kallenborn-Gerhardt
Oct 28, 2019·American Journal of Physiology. Renal Physiology·Adam W WareFiona J McDonald
Nov 30, 2016·The Journal of Biological Chemistry·Christine A KlemensMichael B Butterworth
Jul 13, 2018·Frontiers in Physiology·Adam W WareFiona J McDonald

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