Igloo, a GAP-43-related gene expressed in the developing nervous system of Drosophila

GAP-43 (growth-associated protein, 43 x 10(3) M(r)) is an essential, membrane-associated, neuronal phosphoprotein in vertebrates. The protein is abundantly produced in the growth cones of developing and regenerating neurons, and it is phosphorylated upon induction of long-term potentiation (LTP). Prior work has identified GAP-43-like proteins only in chordates. In this paper, a nervous system-specific gene from Drosophila melanogaster is described that encodes two proteins sharing biochemical activities and sequence homology with GAP-43. The region of homology encompasses the calmodulin-binding domain and protein kinase C (PKC) phosphorylation site of GAP-43. The fly proteins are shown to bind Drosophila calmodulin (CaM), and are phosphorylated by purified PKC after a fashion predicted from prior work with vertebrate GAP-43. GAP-43 is modified by palmitoylation. An amino-terminal myristoylation site is described for the Drosophila protein, which may play a similar role in membrane association in the fly. While a small family of GAP-43-related genes has been recognized in vertebrates, only a single gene appears to be present in the fly. As the Drosophila gene encodes two proteins, each with multiple calmodulin-binding domains and repeated sites for PKC phosphorylation, it may afford functions provided by the family of vertebrate genes.