title: The C-terminal tail domain of metavinculin, vinculin's splice variant, severs actin filaments.
abstract: Vinculin and its splice variant, metavinculin (MV), are key elements of multiple protein assemblies linking the extracellular matrix to the actin cytoskeleton. Vinculin is expressed ubiquitously, whereas MV is mainly expressed in smooth and cardiac muscle tissue. The only difference in amino acid sequence between the isoforms is a 68-residue insert in the C-terminal tail domain of MV (MVt). Although the functional role of this insert remains elusive, its importance is exemplified by point mutations that are associated with dilated and hypertrophic cardiomyopathy. In vinculin, the actin binding site resides in the tail domain. In this paper, we show that MVt binds actin filaments similarly to the vinculin tail domain. Unlike its splice variant, MVt did not bundle actin filaments. Instead, MVt promoted severing of actin filaments, most efficiently at substoichiometric concentrations. This surprising and seemingly contradictory alteration of vinculin function by the 68-residue insert may be essential for modulating compliance of vinculin-induced actin bundles when exposed to rapidly increasing external forces.
authors.affiliation: Bioinformatics and Systems Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Mandy E W
authors.initials: ME
authors.lastname: Janssen
authors.forename: Hongjun
authors.initials: H
authors.lastname: Liu
authors.forename: Niels
authors.initials: N
authors.lastname: Volkmann
authors.forename: Dorit
authors.initials: D
authors.lastname: Hanein
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D017354:Point Mutation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016596:Vinculin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C488955:VCL protein, human; D016596:Vinculin