Rap1 GTPase functions as a regulator of morphogenesis in vivo

• Published in: The EMBO journal Vol. 18; no. 3; pp. 605 - 615
• Main Authors: Asha, H, De Ruiter, N.D, Wang, M.G, Kariharan, I.K
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.1999; Blackwell Publishing Ltd
• Subjects: Amino Acid Sequence; Animals; Binding Sites - genetics; cell differentiation; Cell Division; cell proliferation; cells; compound eyes; Cyclic AMP-Dependent Protein Kinases - metabolism; Drosophila; Drosophila - genetics; Drosophila - growth & development; Drosophila - physiology; Drosophila melanogaster; egg chambers; embryo (animal); embryogenesis; Eye - growth & development; Female; Genes, Insect; genetic complementation; GTP-Binding Proteins - genetics; GTP-Binding Proteins - physiology; GTPase; guanosinetriphosphatase; humans; morphogenesis; Morphogenesis - physiology; mutants; Mutation; nurse cells; ommatidia; Oogenesis; ovaries; ovarioles; Phenotype; Phosphorylation; pyrophosphatases; Rap; rap GTP-Binding Proteins; Ras; ras Proteins - metabolism; Signal Transduction; Species diversity; structural genes; transgenic animals
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1093/emboj/18.3.605

The Ras‐related Rap GTPases are highly conserved across diverse species but their normal biological function is not well understood. Initial studies in 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 activates Rap in vivo. We show that Ras1‐mediated signaling pathways in Drosophila are not influenced by Rap1 levels, suggesting that Ras1 and Rap1 function via distinct pathways. Moreover, a mutation that abolishes the putative cAMP‐dependent kinase phosphorylation site of Drosophila Rap1 can still rescue the Rap1 mutant phenotype. Our experiments show that Rap1 is not needed for cell proliferation and cell‐fate specification but demonstrate a critical function for Rap1 in regulating normal morphogenesis in the eye disk, the ovary and the embryo. Rap1 mutations also disrupt cell migrations and cause abnormalities in cell shape. These findings indicate a role for Rap proteins as regulators of morphogenesis in vivo.