INVERTEBRATE SYNAPSINS - A SINGLE-GENE CODES FOR SEVERAL ISOFORMS IN DROSOPHILA

Vertebrate synapsins constitute a family of synaptic proteins that par ticipate in the regulation of neurotransmitter release, Information on the presence of synapsin homologs in invertebrates has been inconclus ive. We have now cloned a Drosophila gene coding for at least two infe rred proteins that both contain a region with 50% amino acid identity to the highly conserved vesicle- and actin-binding ''C'' domain of ver tebrate synapsins, Within the C domain coding sequence, the positions of two introns have been conserved exactly from fly to human, The posi tions of three additional introns within this domain are similar, The Drosophila synapsin gene (Syn) is widely expressed in the nervous syst em of the fly, The gene products are detected in all or nearly all con ventional synaptic terminals, A single amber (UAG) stop codon terminat es the open reading frame (ORF1) of the most abundant transcript of th e Syn gene 140 amino acid codons downstream of the homology domain. Un expectedly, the stop codon is followed by another 443 in-frame amino a cid codons (ORF2). Using different antibodies directed against ORF1 or ORF2, we demonstrate that in the adult fly small and large synapsin i soforms are generated, The small isoforms are only recognized by antib odies against ORF1; the large isoforms bind both kinds of antibodies, We suggest that the large synapsin isoform in Drosophila may be genera ted by UAG read-through. Implications of such an unconventional mechan ism for the generation of protein diversity from a single gene are dis cussed.