title: Control of actin filament dynamics at barbed ends by WH2 domains: from capping to permissive and processive assembly.
abstract: WH2 domains are multifunctional regulators of actin assembly that can either sequester G-actin or allow polarized barbed end growth. They all bind similarly to a hydrophobic pocket at the barbed face of actin. Depending on their electrostatic environment, WH2 domains can nucleate actin assembly by facilitating the formation of prenuclei dimers along the canonical spontaneous assembly pathway. They also modulate filament barbed end dynamics in a versatile fashion, acting either as barbed end cappers or assisting barbed end growth like profilin or uncapping barbed ends and potentially mediating processive elongation like formins when they are dimerized. Tandem repeats of WH2 domains can sever filaments and either remain bound to created barbed ends like gelsolin, or strip off an ADP-actin subunit from the severed polymer end, depending on their relative affinity for terminal ADP-F-actin or ADP-G-actin. In summary, WH2 domains recapitulate all known elementary regulatory functions so far found in individual actin-binding proteins. By combining different discrete sets of these multifunctional properties, they acquire specific functions in various actin-based processes, and participate in activities as diverse as filament branching, filopodia extension, or actin remodeling in ciliogenesis and asymmetric meiotic division. They also integrate these functions with other actin-binding motifs present either in the same protein or in a complex with another protein, expanding the range of complexity in actin regulation. The details of their molecular mechanisms and the underlying structural basis provide exciting avenues in actin research.
authors.affiliation: Cytoskeleton Dynamics and Motility Team, LEBS, CNRS, Gif-Sur-Yvette, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Carlier
authors.forename: Julien
authors.initials: J
authors.lastname: Pernier
authors.forename: Balendu Sankara
authors.initials: BS
authors.lastname: Avvaru
mesh_terms: D051344:Actin Capping Proteins / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D051304:Profilins / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D051344:Actin Capping Proteins; D008840:Microfilament Proteins; D051304:Profilins
keywords: WH2 domain; actin; filament barbed end assembly