Epithelial sodium channel-mediated sodium transport is not dependent on the membrane-bound serine protease CAP2/Tmprss4

Keppner, Anna; Andreasen, Ditte; Mérillat, Anne-Marie; Bapst, Julie; Ansermet, Camille; Wang, Qing; Maillard, Marc; Malsure, Sumedha; Nobile, Antoine; Hummler, Edith

doi:10.1371/journal.pone.0135224

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Journal article

Epithelial sodium channel-mediated sodium transport is not dependent on the membrane-bound serine protease CAP2/Tmprss4

Keppner, Anna Department of Pharmacology & Toxicology, University of Lausanne, Switzerland
Andreasen, Ditte Department of Pharmacology & Toxicology, University of Lausanne, Switzerland
Mérillat, Anne-Marie Department of Pharmacology & Toxicology, University of Lausanne, Switzerland
Bapst, Julie Department of Pharmacology & Toxicology, University of Lausanne, Switzerland
Ansermet, Camille Department of Pharmacology & Toxicology, University of Lausanne, Switzerland
Wang, Qing Department of Medicine/Physiology, University of Fribourg, Switzerland - Department of Medicine/Division of Nephrology and Hypertension, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Maillard, Marc Department of Medicine/Division of Nephrology and Hypertension, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Malsure, Sumedha Department of Pharmacology & Toxicology, University of Lausanne, Switzerland
Nobile, Antoine Institut Universitaire de Pathologie, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Hummler, Edith Department of Pharmacology & Toxicology, University of Lausanne, Switzerland

26.08.2015

Published in:

PLoS ONE. - 2015, vol. 10, no. 8, p. e0135224

English The membrane-bound serine protease CAP2/Tmprss4 has been previously identified in vitro as a positive regulator of the epithelial sodium channel (ENaC). To study its in vivo implication in ENaC-mediated sodium absorption, we generated a knockout mouse model for CAP2/Tmprss4. Mice deficient in CAP2/Tmprss4 were viable, fertile, and did not show any obvious histological abnormalities. Unexpectedly, when challenged with sodium-deficient diet, these mice did not develop any impairment in renal sodium handling as evidenced by normal plasma and urinary sodium and potassium electrolytes, as well as normal aldosterone levels. Despite minor alterations in ENaC mRNA expression, we found no evidence for altered proteolytic cleavage of ENaC subunits. In consequence, ENaC activity, as monitored by the amiloride-sensitive rectal potential difference (ΔPD), was not altered even under dietary sodium restriction. In summary, ENaC-mediated sodium balance is not affected by lack of CAP2/Tmprss4 expression and thus, does not seem to directly control ENaC expression and activity in vivo.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

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