Article

The Rho Family GTPase Rif Induces Filopodia through mDia2

Mammalian Cell Biology Laboratory, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
Current Biology (Impact Factor: 9.92). 02/2005; 15(2):129-33. DOI: 10.1016/j.cub.2005.01.011
Source: PubMed

ABSTRACT 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.

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Available from: Harry Mellor, Aug 23, 2015
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    • "Factors such as VASP family members or ill-defined components of the filopodia tip complex may then promote the transient association of actin filaments, which can be further stabilized by other bundlers, such as fascin, thus permitting the formation of actin bundles and filopodia (Mogilner & Rubinstein, 2005). According to the de novo nucleation model, formins (Pellegrin & Mellor, 2005; Schirenbeck et al., 2005; Yang et al., 2007; Block et al., 2008) or VASP tetramers, particularly when clustered along the plasma membrane (Breitsprecher et al., 2008, 2011; Hansen & Mullins, 2010), may be responsible for promoting filopodial initiation. Also in this case, however, filaments must be protected from cappers, which have been shown, in the case of the capping protein (CP), to compete, either directly or indirectly, with VASP as well as with formins for barbed-end binding (Breitsprecher et al., 2008). "
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