IDENTIFICATION OF A NEURONAL CALMODULIN-BINDING PEPTIDE, CAP-19, CONTAINING AN IQ MOTIF

Neurons produce polypeptides which can bind the calcium-poor or pre-ac tivated form of calmodulin. It is expected that this class of peptide will serve an important role in maintaining cellular homeostasis since it would modulate calcium-dependent target regulation and redirect in tracellular signaling. The lack of conserved sequence has made the ide ntification of these peptides difficult, consequently leading us to ex ploit their property of binding calcium-poor calmodulin as a means of finding new species, A new peptide termed Calmodulin-Associated Peptid e-19 (CAP-19) was purified and characterized. The protein-sequence inf ormation was employed in order to recover a cDNA clone from rat which included the entire reading frame for the peptide. Like its counterpar ts, neuromodulin (GAP-43), neurogranin (RC3) and PEP-19, it contains a n IQ motif although the remainder of the peptide is quite different. N orthern blot analysis of ribonucleic acid (RNA) from animals of differ ing ages indicated that the message appears at birth and then persists into adulthood. Antibodies to synthetic peptide were employed for loc alizing CAP-19. The results indicated that the peptide was localized t o neurons in several brain regions. CAP-19 is similar to other calmodu lin-binding proteins in that the domain spanning the IQ motif was demo nstrated to participate in binding to calmodulin. Database searching s howed CAP-19 to be homologous to the silkworm protein, multiprotein br idging factor 1 (MBF1), This homology suggests a potential new role fo r calmodulin-associated proteins in cellular homeostasis. (C) 1998 Els evier Science B.V. All rights reserved.