Generation of branched actin networks: assembly and regulation of the N-WASP and WAVE molecular machines.
The Arp2/3 complex is a molecular machine that generates branched actin networks responsible for membrane remodeling during cell migration, endocytosis, and other morphogenetic events. This machine requires activators, which themselves are multiprotein complexes. This review focuses on recent advances concerning the assembly of stable complexes containing the most-studied activators, N-WASP and WAVE proteins, and the level of regulation that is provided by these complexes. N-WASP is the paradigmatic auto-inhibited protein, which is activated by a conformational opening. Even though this regulation has been successfully reconstituted in vitro with isolated N-WASP, the native dimeric complex with a WIP family protein has unique additional properties. WAVE proteins are part of a pentameric complex, whose basal state and activated state when bound to the Rac GTPase were recently clarified. Moreover, this review attempts to put together diverse observations concerning the WAVE complex in the conceptual frame of an in vivo assembly pathway that has gained support from the recent identification of a precursor.
Derivery
Emmanuel
E
CNRS UPR3082, Laboratoire d'Enzymologie et de Biochimie Structurales, Bât. 34, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
Gautreau
Alexis
A
D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal