The Rho family GTPase Rif induces filopodia through mDia2.
Eukaryotic cells produce a variety of specialized actin-rich surface protrusions. These include filopodia-thin, highly dynamic projections that help cells to sense their external environment. Filopodia consist of parallel filaments of actin, bundled by actin crosslinking proteins. The filaments are oriented with their rapidly growing "barbed" ends at the protruding tip and their slowly growing "pointed" ends at the base. Extension occurs by polymerization at the tip and is controlled by regulation of filament capping. The Rho GTPase Cdc42 is a key mediator of filopodia formation, which it regulates through binding CRIB domain-containing effectors. Cdc42 binds and activates the WASP proteins, which in turn activate the actin-nucleating complex Arp2/3. It also binds and activates IRSp53, which recruits the Ena/WASP family protein Mena to the filopodial tip and protects elongating actin filaments from capping. Previously, we identified another Rho family GTPase, Rif, as a potent stimulator of filopodial protrusion through a mechanism that does not require Cdc42. Here we characterize the differences between filopodia induced by these two small GTPases and show that the Rif effector in this pathway is the Diaphanous-related formin mDia2. Thus, Rif and Cdc42 represent two distinct routes to the induction of filopodia-producing structures with both shared and unique properties.
Pellegrin
Stéphanie
S
Mammalian Cell Biology Laboratory, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom. s.pellegrin@bristol.ac.uk
Mellor
Harry
H
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D011554:Pseudopodia / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D002352:Carrier Proteins; C491463:Diap2 protein, mouse; D000080865:Formins; C419867:RHOF protein, human; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins