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

Autor:	Noriega LG; Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Melo Z; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; CONACYT-Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico., Rajaram RD; Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.; National Centre of Competence in Research, 'Kidney.ch', Zurich, Switzerland., Mercado A; Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico., Tovar AR; Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Velazquez-Villegas LA; Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Castañeda-Bueno M; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Reyes-López Y; Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Ryu D; Laboratory of Integrative and Systems Physiology (LISP), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Rojas-Vega L; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Magaña-Avila G; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., López-Barradas AM; Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Sánchez-Hernández M; Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico., Debonneville A; Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.; National Centre of Competence in Research, 'Kidney.ch', Zurich, Switzerland., Doucet A; Centre de Recherche des Cordeliers, INSERM, Sorbonne Universités, USPC, Université Paris Descartes, Université Paris Diderot, Physiologie Rénale et Tubulopathies, CNRS ERL 8228, Paris, France., Cheval L; Centre de Recherche des Cordeliers, INSERM, Sorbonne Universités, USPC, Université Paris Descartes, Université Paris Diderot, Physiologie Rénale et Tubulopathies, CNRS ERL 8228, Paris, France., Torres N; Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Auwerx J; Laboratory of Integrative and Systems Physiology (LISP), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Staub O; Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.; National Centre of Competence in Research, 'Kidney.ch', Zurich, Switzerland., Gamba G; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2021 May 05; Vol. 22 (5), pp. e50766. Date of Electronic Publication: 2021 Mar 22.
DOI:	10.15252/embr.202050766
Abstrakt:	SIRT7 is a NAD + -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 + -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. (© 2021 The Authors.)
Databáze:	MEDLINE
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