the dock protein sponge binds to elmo and functions in drosophila embryonic cns developmentdock蛋白海绵结合艾尔摩在果蝇胚胎中枢神经系统发展和功能.pdf

The DOCK Protein Sponge Binds to ELMO and Functions in Drosophila Embryonic CNS Development 1,2 1,2 1 1 Bridget Biersmith , Ze (Cindy) Liu , Kenneth Bauman , Erika R. Geisbrecht * 1 Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri, Kansas City, Missouri, United States of America, 2 Ph.D. Program, School of Biological Sciences, University of Missouri, Kansas City, Missouri, United States of America Abstract Cell morphogenesis, which requires rearrangement of the actin cytoskeleton, is essential to coordinate the development of tissues such as the musculature and nervous system during normal embryonic development. One class of signaling proteins that regulate actin cytoskeletal rearrangement is the evolutionarily conserved CDM (C. elegans Ced-5, human DOCK180, Drosophila Myoblast city, or Mbc) family of proteins, which function as unconventional guanine nucleotide exchange factors for the small GTPase Rac. This CDM-Rac protein complex is sufficient for Rac activation, but is enhanced upon the association of CDM proteins with the ELMO/Ced-12 family of proteins. We identified and characterized the role of Drosophila Sponge (Spg), the vertebrate DOCK3/DOCK4 counterpart as an ELMO-interacting protein. Our analysis shows Spg mRNA and protein is expressed in the visceral musculature and developing nervous system, suggesting a role for Spg in later embryogenesis. As maternal null mutants of spg die early in development, we utilized genetic interaction analysis to uncover the role of Spg in central nervous system (CNS) development. Consistent with its role in ELMO-dependent pathways, we found genetic interactions wit