Rab35 Controls Actin Bundling by Recruiting Fascin as an Effector Protein
Fascin-Actin Rab Bristles
Rab proteins have diverse functions in directing intracellular traffic and may also affect development. Zhang et al. (p. 1250) show that during Drosophila development Rab35 influences the development of bristles, neurosensory structures built upon bundled actin. Rab35 also caused massive actin-rich filopodia protrusions from cultured cells. Activated Rab35 interacted directly with fascin, an actin filament bundling protein, to colocalize near the plasma membrane. When Rab35 was engineered to interact with the surface of mitochondria, it stimulated localized actin assembly in a fascin-dependent manner. Thus, fascin is a Rab35 effector protein that links membrane trafficking regulation to cytoskeleton assembly during development.
Abstract
Actin filaments are key components of the eukaryotic cytoskeleton that provide mechanical structure and generate forces during cell shape changes, growth, and migration. Actin filaments are dynamically assembled into higher-order structures at specified locations to regulate diverse functions. The Rab family of small guanosine triphosphatases is evolutionarily conserved and mediates intracellular vesicle trafficking. We found that Rab35 regulates the assembly of actin filaments during bristle development in Drosophila and filopodia formation in cultured cells. These effects were mediated by the actin-bundling protein fascin, which directly associated with active Rab35. Targeting Rab35 to the outer mitochondrial membrane triggered actin recruitment, demonstrating a role for an intracellular trafficking protein in localized actin assembly.
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Published In
Science
Volume 325 | Issue 5945
4 September 2009
4 September 2009
Copyright
Copyright © 2009, American Association for the Advancement of Science.
Submission history
Received: 13 April 2009
Accepted: 10 July 2009
Published in print: 4 September 2009
Acknowledgments
We thank M. Fish for DNA injections; X. Huang, E. Bustamante, and C. Gauthier for help with initial experiments; Scott lab members for valuable discussion and comments; the Stanford Cell Sciences Imaging Facility for assistance with scanning electron microscopy studies; and S. Pfeffer, A. Ghabrial, and R. Rohatgi for critical reading and comments on the manuscript. Supported by a Jane Coffin Childs Memorial Fund for Medical Research fellowship (J.Z.) and by the NIH National Technology Center for Networks and NIH Pathway grant U54 RR020843 (M.F. and M.B.). The research reported here was supported by the Howard Hughes Medical Institute. M.P.S. is an Investigator of the HHMI.
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