Molecular analysis of novel Drosophila gene, Gap69C, encoding a homolog of ADP-ribosylation factor GTPase-activating protein.

Adenosine diphosphate-ribosylation factor, ARF1, regulates membrane traffic and structure in the endoplasmic reticulum-Golgi and endosomal systems. The ARF activity, in turn, is regulated by the guanine nucleotide exchange factors and GTPase-activating proteins (GAPs). We have cloned by transposon tagging a novel Drosophila gene, Gap69C, coding for a putative homolog of ARF1 GTPase-activating protein. The GAP69C protein shares an extensive similarity within its N-terminal zinc-finger domain with the rat and yeast homologs. This domain is known to be required for ARF-GAP activity. The Gap69C is a single-copy gene producing a major 2.1-kb mRNA throughout development, but its amount is decreased in larvae. The eye pigmentation produced by the reporter mini-white gene inserted into the 5' UTR of Gap69C suggests that the expression of Gap69C is nonuniform. In situ hybridization revealed a high level of Gap69C transcripts in the morphogenetic furrow of the eye imaginal disc, where cells are arrested in G(1). Generated by the excision of the P-element, the null allele of Gap69C was found to be viable and fertile and showed no apparent abnormal phenotype, indicating that Gap69C is not essential for fly development. Analysis of the Drosophila genome sequence revealed the presence of other genes related to Gap69C. We propose that the absence of a distinctive phenotype in Gap69C null mutants is attributable to redundancy with other homologs.