Article (Scientific journals)
Ubiquitous and kidney-specific subunits of vacuolar H+-ATPase are differentially expressed during nephrogenesis.
JOURET, François; Auzanneau, Celine; Debaix, Huguette et al.
2005In Journal of the American Society of Nephrology, 16 (11), p. 3235-46
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Keywords :
Animals; Base Sequence; DNA Primers; Embryonic Development; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Genes, Reporter; In Situ Hybridization; Isoenzymes/metabolism; Kidney/enzymology; Kidney Tubules/enzymology; Mice; Oligonucleotide Probes; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Vacuolar Proton-Translocating ATPases/genetics/metabolism
Abstract :
[en] The vacuolar H(+)-ATPase (V-ATPase) is a ubiquitous multisubunit pump that is responsible for acidification of intracellular organelles. In the kidney, a particular form of V-ATPase, made of specific subunits isoforms, has been located at the plasma membrane of intercalated cells (IC). Mutations in genes encoding IC-specific subunits cause infant distal renal tubular acidosis (dRTA), suggesting that the segmental distribution of these subunits is acquired at birth or during early infancy. However, the comparative ontogeny of the IC-specific versus the ubiquitous subunits of V-ATPase and the mechanisms involved in their segmental expression remain unknown. Real-time reverse transcription-PCR, in situ hybridization, immunoblotting, immunostaining, and subcellular fractionation analyses characterized the expression and distribution of V-ATPase subunits, transcription factors, and differentiation markers during mouse nephrogenesis. Ubiquitous A, E1, B2, G1, and C1 subunits showed an early (embryonic day 13.5 [E13.5]) and stable expression throughout nephrogenesis, followed by a slight increase around birth. The developmental pattern of a1 was bimodal, with early induction, gradual decrease during organogenesis, and neonatal increase. These patterns contrasted with the later (from E15.5) and progressive expression of IC-specific a4, B1, G3, and C2 subunits, after the induction of the forkhead transcription factor Foxi1. From E15.5, Foxi1 mRNA was detected in IC, where it co-distributed with B1 in late nephrogenesis. Immunostaining showed that the distribution of ubiquitous E1 and B2 was acquired from E15.5, whereas a4 was located in IC during late nephrogenesis. Subcellular fractionation showed that in both fetal and mature (cortex and medulla) kidneys, E1 and a4 were located in endosomes. These data demonstrate a differential expression and a coordinate regulation of IC-specific versus ubiquitous V-ATPase subunits during nephrogenesis. They provide new insights into the complex regulation of V-ATPase subunits, the maturation of IC along the nephron, and the pathophysiology of hereditary dRTA.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
JOURET, François  ;  Centre Hospitalier Universitaire de Liège - CHU > Néphrologie
Auzanneau, Celine
Debaix, Huguette
Wada, Ge-Hong Sun
Pretto, Chrystel
Marbaix, Etienne
Karet, Fiona E.
Courtoy, Pierre J.
Devuyst, Olivier
Language :
English
Title :
Ubiquitous and kidney-specific subunits of vacuolar H+-ATPase are differentially expressed during nephrogenesis.
Publication date :
2005
Journal title :
Journal of the American Society of Nephrology
ISSN :
1046-6673
eISSN :
1533-3450
Publisher :
Lippincott Williams and Wilkins, Washington, United States - District of Columbia
Volume :
16
Issue :
11
Pages :
3235-46
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 21 November 2012

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