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Mol Cell Biol. 2010 Dec;30(24):5649-57. doi: 10.1128/MCB.00635-10. Epub 2010 Oct 11.

Cytosolic Ras supports eye development in Drosophila.

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1
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.

Abstract

Ras proteins associate with cellular membranes as a consequence of a series of posttranslational modifications of a C-terminal CAAX sequence that include prenylation and are thought to be required for biological activity. In Drosophila melanogaster, Ras1 is required for eye development. We found that Drosophila Ras1 is inefficiently prenylated as a consequence of a lysine in the A(1) position of its CAAX sequence such that a significant pool remains soluble in the cytosol. We used mosaic analysis with a repressible cell marker (MARCM) to assess if various Ras1 transgenes could restore photoreceptor fate to eye disc cells that are null for Ras1. Surprisingly, we found that whereas Ras1 with an enhanced efficiency of membrane targeting could not rescue the Ras1 null phenotype, Ras1 that was not at all membrane targeted by virtue of a mutation of the CAAX cysteine was able to fully rescue eye development. In addition, constitutively active Ras1(12V,C186S) not targeted to membranes produced a hypermorphic phenotype and stimulated mitogen-activated protein kinase (MAPK) signaling in S2 cells. We conclude that the membrane association of Drosophila Ras1 is not required for eye development.

PMID:
20937772
PMCID:
PMC3004281
DOI:
10.1128/MCB.00635-10
[Indexed for MEDLINE]
Free PMC Article
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