The Rap1 GTPase functions as a regulator of morphogenesis in vivo

The Ras-related Rap GTPases are highly conserved across diverse species but their normal biological function is not well understood. Initial studies i n mammalian cells suggested a role for Rap as a Ras antagonist. More recent experiments indicate functions in calcium- and cAMP-mediated signaling and it has been proposed that protein kinase A-mediated phosphorylation activa tes Rap in vivo. We show that Ras1-mediated signaling pathways in Drosophil a are not influenced by Rap1 levels, suggesting that Ras1 and Rap2 function via distinct pathways. Moreover, a mutation that abolishes the putative cA MP-dependent kinase phosphorylation site of Drosophila Rap1 can still rescu e the Rap1 mutant phenotype. Our experiments show that Rap1 is not needed f or cell proliferation and cell-fate specification but demonstrate a critica l function for Rap1 in regulating normal morphogenesis in the eye disk, the ovary and the embryo. Rap1 mutations also disrupt cell migrations and caus e abnormalities in cell shape. These findings indicate a role for Rap prote ins as regulators of morphogenesis in vivo.