Drosophila rab GDI mutants disrupt development but have normal rab membrane extraction

Rab GTPases are essential for vesicular transport. Rab GDP dissociation inh ibitor (GDI) binds to GDP-bound rabs, removes rabs from acceptor membranes and delivers rabs to donor membranes. We isolated lethal GDI mutations in D rosophila and analyzed their developmental phenotypes. To learn how these m utations affect GDI structure, the crystal structure of Drosophila GDI was determined by molecular replacement to a resolution of 3.0 Angstrom. Two hy pomorphic, missense mutations are located in domain II of GDI at highly con served positions, but not in previously identified sequence conserved regio ns. The mutant GDIs were tested for ability to extract rabs from membranes and showed wild-type levels of rab membrane extraction. The two missense al leles showed intragenic complementation, indicating that domain II of GDI m ay have two separable functions. This study indicates that GDI function is essential for development of a complex, multicellular organism and that pup arium formation and pole cell formation are especially dependent on GDI fun ction. (C) 2001 Wiley-Liss, Inc.