Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity

Elodie Ehret
ORCID logo ,
Sévan Stroh
,
Muriel Auberson
ORCID logo ,
Frédérique Ino
,
Yannick Jäger
,
Marc Maillard
,
Roman Szabo
,
Thomas H Bugge
,
Simona Frateschi
,
Edith Hummler
* ORCID logo
Version 1 : Received: 11 August 2023 / Approved: 11 August 2023 / Online: 14 August 2023 (10:10:56 CEST)

A peer-reviewed article of this Preprint also exists.

Ehret, E.; Stroh, S.; Auberson, M.; Ino, F.; Jäger, Y.; Maillard, M.; Szabo, R.; Bugge, T.H.; Frateschi, S.; Hummler, E. Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity. Cells 2023, 12, 2342. Ehret, E.; Stroh, S.; Auberson, M.; Ino, F.; Jäger, Y.; Maillard, M.; Szabo, R.; Bugge, T.H.; Frateschi, S.; Hummler, E. Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity. Cells 2023, 12, 2342.

Abstract

The serine proteases CAP1/Prss8 (prostasin) and CAP3/St14 (matriptase) are identified as ENaC channel-activating proteases in vitro highly suggesting that they are required for proteolytic activation of ENaC in vivo. The present study tested whether CAP3 is relevant for renal proteolytic ENaC activation and affects ENaC-mediated Na+ absorption following Na+-deprivation conditions. CAP3 knockout mice exhibit significant decrease in CAP1 protein expression with altered ENaC subunit and decreased pNCC protein abundances, but overall maintain sodium balance. RNAscope-based analyses reveal co-expression of CAP3 and CAP1 with alpha ENaC in distal tubules of the cortex from wildtype mice. Double CAP1/CAP3-deficiency maintained Na+ and K+ balance on Na+-deprived diet, restored ENaC subunit protein abundances but showed reduced NCC activity under Na+-deprivation. Overall, our data clearly show that CAP3 is not required for direct proteolytic activation of ENaC, but for its protein abundances. Our study reveal a complex regulation of ENaC by these serine proteases on the expression level rather than on its proteolytic activation.

Keywords

Proteolytic ENaC activation; Prss8; St14; sodium and potassium balance

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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