THE SEA-URCHIN SPERM RECEPTOR FOR EGG JELLY IS A MODULAR PROTEIN WITHEXTENSIVE HOMOLOGY TO THE HUMAN POLYCYSTIC KIDNEY-DISEASE PROTEIN, PKD1

During fertilization, the sea urchin sperm acrosome reaction (AR), an ion channel-regulated event, is triggered by glycoproteins in egg jell y (EJ). A 210-kD sperm membrane glycoprotein is the receptor for EJ (R EJ). This conclusion is based on the following data: purified REJ bind s species specifically to EJ dotted onto nitrocellulose, an mAb to REJ induces the sperm AR, antibody induction is blocked by purified REJ, and purified REJ absorbs the AR-inducing activity of EJ. Overlapping f ragments of REJ cDNA were cloned (total length, 5,596 bp). The sequenc e was confirmed by microsequencing six peptides of mature REJ and by W estern blotting with antibody to a synthetic peptide designed from the sequence. Complete deglycosylation of REJ followed by Western blottin g yielded a size estimate in agreement with that of the mature amino a cid sequence. REJ is modular in design; it contains one EGF module and two C-type lectin carbohydrate-recognition modules, Most importantly, it contains a novel module, herein named the REJ module (700 residues ), which shares extensive homology with the human polycystic kidney di sease protein (PKD1). Mutations in PKD1 cause autosomal dominant polyc ystic kidney disease, one of the most frequent genetic diseases of hum ans. The lesion in cellular physiology resulting from mutations in the PKD1 protein remains unknown. The homology between REJ modules of the sea urchin REJ and human PKD1 suggests that PKD1 could be involved in ionic regulation.