SIRT7 modulates the stability and activity of the renal K-Cl cotransporter KCC4 through deacetylation.

Details

Serval ID
serval:BIB_5D3DFB594146
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
SIRT7 modulates the stability and activity of the renal K-Cl cotransporter KCC4 through deacetylation.
Journal
EMBO reports
Author(s)
Noriega L.G., Melo Z., Rajaram R.D., Mercado A., Tovar A.R., Velazquez-Villegas L.A., Castañeda-Bueno M., Reyes-López Y., Ryu D., Rojas-Vega L., Magaña-Avila G., López-Barradas A.M., Sánchez-Hernández M., Debonneville A., Doucet A., Cheval L., Torres N., Auwerx J., Staub O., Gamba G.
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Publication state
Published
Issued date
05/05/2021
Peer-reviewed
Oui
Volume
22
Number
5
Pages
e50766
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
SIRT7 is a NAD <sup>+</sup> -dependent deacetylase that controls important aspects of metabolism, cancer, and bone formation. However, the molecular targets and functions of SIRT7 in the kidney are currently unknown. In silico analysis of kidney transcripts of the BXD murine genetic reference population revealed a positive correlation between Sirt7 and Slc12a7 mRNA expression, suggesting a link between the corresponding proteins that these transcripts encode, SIRT7, and the K-Cl cotransporter KCC4, respectively. Here, we find that protein levels and activity of heterologously expressed KCC4 are significantly modulated depending on its acetylation status in Xenopus laevis oocytes. Moreover, SIRT7 interacts with KCC4 in a NAD <sup>+</sup> -dependent manner and increases its stability and activity in HEK293 cells. Interestingly, metabolic acidosis increases SIRT7 expression in kidney, as occurs with KCC4. In contrast, total SIRT7-deficient mice present lower KCC4 expression and an exacerbated metabolic acidosis than wild-type mice during an ammonium chloride challenge. Altogether, our data suggest that SIRT7 interacts with, stabilizes and modulates KCC4 activity through deacetylation, and reveals a novel role for SIRT7 in renal physiology.
Keywords
Acetylation, Animals, HEK293 Cells, Humans, Kidney, Mice, Sirtuins/genetics, Sirtuins/metabolism, Symporters/genetics, Symporters/metabolism, kidney tubule, renal tubular acidosis, sirtuins
Pubmed
Web of science
Create date
30/03/2021 11:55
Last modification date
06/07/2021 6:36
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