Secretion of mouse ZP3, the sperm receptor, requires cleavage of its polypeptide at a consensus furin cleavage-site

The mouse egg extracellular coat, or zona pellucida, consists of three glyc oproteins, called mZP1-3, Each glycoprotein possesses a consensus sequence recognized by the furin family of proprotein convertases. Previously, it wa s reported that mZP2 and mZP3 are cleaved at their consensus furin cleavage -sites located near the C-terminus of the polypeptides [Litscher, E. S., Qi , H., and Wassarman, P. M. (1999) Biochemistry 38, 12280-12287]. Here, use of site-directed mutagenesis of the mZP3 gene and a specific inhibitor of f urin-like enzymes revealed that secretion of nascent mZP3 from transfected cells is dependent on cleavage of mZP3 at its consensus furin cleavage-site . The dependence of secretion on cleavage represents a novel function for f urin family enzymes.