Molecular mechanisms of cutis laxa- and distal renal tubular acidosis-causing mutations in V-ATPase a subunits, ATP6V0A2 and ATP6V0A4.

The Journal of Biological Chemistry
Sally EsmailMorris F Manolson

Abstract

The a subunit is the largest of 15 different subunits that make up the vacuolar H+-ATPase (V-ATPase) complex, where it functions in proton translocation. In mammals, this subunit has four paralogous isoforms, a1-a4, which may encode signals for targeting assembled V-ATPases to specific intracellular locations. Despite the functional importance of the a subunit, its structure remains controversial. By studying molecular mechanisms of human disease-causing missense mutations within a subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation. cDNA-encoded FLAG-tagged human wildtype ATP6V0A2 (a2) and ATP6V0A4 (a4) subunits and their mutants, a2P405L (causing cutis laxa), and a4R449H and a4G820R (causing renal tubular acidosis, dRTA), were transiently expressed in HEK 293 cells. N-Glycosylation was assessed using endoglycosidases, revealing that a2P405L, a4R449H, and a4G820R were fully N-glycosylated. Cycloheximide (CHX) chase assays revealed that a2P405L and a4R449H were unstable relative to wildtype. a4R449H was degraded predominantly in the proteasomal pathway, whereas a2P405L was degraded in both proteasomal and lysosomal pathways. Immunofluorescence studies disclosed retention in the ...Continue Reading

References

Sep 10, 2004·Molecular Biology of the Cell·Per MalkusRandy Schekman
Sep 24, 2004·Physiological Reviews·Carsten A WagnerJohn P Geibel
Jan 18, 2006·Nature Cell Biology·Andrés Hurtado-LorenzoVladimir Marshansky
Feb 2, 2006·The Journal of Experimental Biology·Klaus W Beyenbach, Helmut Wieczorek
Oct 4, 2007·Nature Reviews. Molecular Cell Biology·Michael Forgac
Nov 21, 2007·Pflügers Archiv : European journal of physiology·Ayana HintonMichael Forgac
Sep 19, 2008·Molecular Biology of the Cell·Margret RyanTom H Stevens
Jan 28, 2009·Biochimica Et Biophysica Acta·Mailys GuillardRon A Wevers
Dec 10, 2009·Nature Reviews. Molecular Cell Biology·Joseph R CaseyJohn Orlowski
Jan 14, 2010·Current Protocols in Molecular Biology·Hudson H Freeze, Christian Kranz
May 11, 2010·Biochemistry·Masashi ToeiMichael Forgac
Apr 21, 2011·Bioinformatics·Joost Van DurmeFrederic Rousseau
Mar 31, 2012·Biochimica Et Biophysica Acta·Masamitsu FutaiRobert K Nakamoto
Jun 12, 2012·The Journal of Biological Chemistry·Ajay BhargavaMorris F Manolson
Jul 10, 2012·Human Genetics·Björn FischerUwe Kornak
Nov 2, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Daniel Batlle, Syed K Haque
Jan 9, 2013·Journal of Cellular Biochemistry·Norbert KartnerMorris F Manolson
Jan 15, 2013·Acta Neuropathologica·Nivetha RamachandranBerge A Minassian
May 15, 2013·Nature Chemical Biology·Tsukasa OkiyonedaGergely L Lukacs
Jul 24, 2013·Nature Reviews. Endocrinology·Cristina SobacchiMiep H Helfrich
Sep 3, 2013·Physiology·Sylvie Breton, Dennis Brown
Sep 13, 2013·International Journal of Molecular Sciences·Mariana G Bexiga, Jeremy C Simpson
Jan 8, 2014·Disease Models & Mechanisms·Julie S Valastyan, Susan Lindquist
May 2, 2014·Nucleic Acids Research·Marco BiasiniTorsten Schwede
Jan 7, 2015·BMC Genomics·Jose Guevara-CotoLiangjiang Wang
Mar 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Daniel G SchepJohn L Rubinstein
Nov 4, 2016·Nature·Mohammad T Mazhab-JafariJohn L Rubinstein

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Citations

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Jan 24, 2021·Medicinal Research Reviews·Cátia Santos-PereiraManuela Côrte-Real
Feb 1, 2020·Trends in Biochemical Sciences·Thamiya Vasanthakumar, John L Rubinstein
May 19, 2020·Biochimica Et Biophysica Acta. Biomembranes·Michael P Collins, Michael Forgac
Jul 7, 2020·Cellular Signalling·Xuesong Chen, Jonathan D Geiger
Apr 8, 2019·The American Journal of Pathology·Biswajit KhatuaVijay P Singh

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