8.A.131. The Transmembrane Protease Serine (TMPRSS) Family
TMPRSS3 is a serine protease that plays a role in hearing. It acts as a permissive factor for cochlear hair cell survival and activation at the onset of hearing and is required for saccular hair cell survival. It activates ENaC channels (Guipponi et al. 2002). Important signaling pathways in the inner ear are controlled by proteolytic cleavage and suggest: (i) the existence of an auto-catalytic processing by which TMPRSS3 becomes active, and (ii) that ENaC is a substrate of TMPRSS3 in the inner ear. Missense mutations in TMPRSS3 greatly diminish the proteolytic activity of TMPRSS3, and this explains the importance of the protease in nonsyndromic hearing loss (NSHL) (Wong et al. 2020).
Corin of Homo sapiens is a protease of 1042 aas with an N-terminal TMS, also called atrial natriuretic peptide-converting enzyme. It is a serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing (Yan et al. 2000, Jiang et al. 2011, Peng et al. 2011). It converts through proteolytic cleavage the non-functional propeptides NPPA and NPPB into their active hormones, ANP and BNP(1-32), respectively, thereby regulating blood pressure in the heart and promoting natriuresis, diuresis and vasodilation (Yan et al. 2000). Proteolytic cleavage of pro-NPPA also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus (Cui et al. 2012). CRN also acts as a regulator of sodium reabsorption in the kidney. It is inhibited in a dose-dependent manner by non-specific trypsin-like serine protease inhibitors including benzamidine. It regulates electrolyte homeostasis in eccrine sweat glands (He et al. 2021).