Neprilysin II: A putative novel metalloprotease and its isoforms in CNS and testis

Metalloproteases of the M13 subfamily, comprising namely neprylisin (NEP) a nd endothelin-converting enzyme (ECE), are involved in the metabolism of va rious neuronal and hormonal peptides, and inhibitors thereof have already Z ed to therapeutically useful agents. Using homology cloning, we have identi fied a new member of this family in rat tissues. It is a glycosylated, type II integral membrane protein of 774 amino acids, containing a zinc-binding consensus motif, highly homologous to NEP and, therefore, designated NEPII . We have characterized multiple splice variants of NEPII mRNA with distinc t expression patterns in brain regions, pituitary and testis. In situ hybri dization of testis, where levels of the NEPII gene transcript are the highe st, reveals a localization within round spermatids. In brain, NEPII is expr essed heterogeneously among several neuronal populations and according to a pattern grossly complementary to that of NEP. (C) 2000 Academic Press.