DISTINCTIVE SUBTYPES OF BOVINE PHOSPHOLIPASE-C THAT HAVE PREFERENTIALEXPRESSION IN THE RETINA AND HIGH HOMOLOGY TO THE NORPA GENE-PRODUCT OF DROSOPHILA

The Drosophila norpA gene encodes a phospholipase C involved in photot ransduction. However, phospholipase C apparently is not directly invol ved in phototransduction in vertebrate photoreceptors, although light- activated phospholipase C activity has been reported in vertebrate rod outer segments. Conserved regions of norpA cDNA were used to isolate bovine cDNAs that would encode four alternative forms of phospholipase C of the beta class that are highly homologous to the norpA protein a nd expressed preferentially in the retina. Two of the variants are hig hly unusual in that they lack much of the N-terminal region present in all other known phospholipases C. The sequence conservation between t hese proteins and the norpA protein is higher than that between any ot her known phospholipases C. GTPase sequence motifs found in proteins o f the GTPase superfamily are found conserved in all four variants of t he bovine retinal protein as well as the norpA protein but not in othe r phospholipases C. Results suggest that these proteins together with the norpA protein constitute a distinctive subfamily of phospholipases C that are closely related in structure, function, and tissue distrib ution. Mutations in the norpA gene, in addition to blocking phototrans duction, cause light-dependent degeneration of photoreceptors. In view of the strong similarity in structure and tissue distribution, a defe ct in these proteins may have similar consequences in the mammalian re tina.