Journal article
Regulation of Drosophila mesoderm migration by phosphoinositides and the PH domain of the Rho GTP exchange factor Pebble
MJ Murray, MM Ng, H Fraval, J Tan, W Liu, M Smallhorn, JA Brill, SJ Field, R Saint
Developmental Biology | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2012
Abstract
The Drosophila RhoGEF Pebble (Pbl) is required for cytokinesis and migration of mesodermal cells. In a screen for genes that could suppress migration defects in pbl mutants we identified the phosphatidylinositol phosphate (PtdInsP) regulator pi5k59B. Genetic interaction tests with other PtdInsP regulators suggested that PtdIns(4,5)P2 levels are important for mesoderm migration when Pbl is depleted. Consistent with this, the leading front of migrating mesodermal cells was enriched for PtdIns(4,5)P2. Given that Pbl contains a Pleckstrin Homology (PH) domain, a known PtdInsP-binding motif, we examined PtdInsP-binding of Pbl and the importance of the PH domain for Pbl function. In vitro lipid bl..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank J. Wang and A. Srivastava for help with the EP screen and A. Wilkes, U. Wiedemann and N. Lorensuhewa for assistance in cloning. We thank L. Cooley and L. Jones for fly lines and the pUB-2-GFP-PH<SUP>PLC partial derivative</SUP> plasmid. We thank J. Milverton for transgenic injections. We thank B. Edgar, H. Bellen, H. Richardson and the Bloomington stock centre for fly stocks. Antibodies were kindly provided by M. Leptin, D. Kiehart, H. Bellen, S. Roth and the Developmental Studies Hybridoma Bank. This work was supported by a RESTRACOMP scholarship from The Hospital for Sick Children (to J. T.), an operating grant from The Cancer Research Society, Inc. (to J. A. B.); the ARC Special Research Centre for the Molecular Genetics of Development. NHMRC project grant 316959 (to M.J.M. and R.S) and ARC Discovery Grant DP0987338 (to R.S.); S.J.F. acknowledges support from NIH New Innovator Award DP2OD004265 and R01CA138676. M.M.N. acknowledges support from the American Cancer Society.