title: Leiomodin is an actin filament nucleator in muscle cells.
abstract: Initiation of actin polymerization in cells requires nucleation factors. Here we describe an actin-binding protein, leiomodin, that acted as a strong filament nucleator in muscle cells. Leiomodin shared two actin-binding sites with the filament pointed end-capping protein tropomodulin: a flexible N-terminal region and a leucine-rich repeat domain. Leiomodin also contained a C-terminal extension of 150 residues. The smallest fragment with strong nucleation activity included the leucine-rich repeat and C-terminal extension. The N-terminal region enhanced the nucleation activity threefold and recruited tropomyosin, which weakly stimulated nucleation and mediated localization of leiomodin to the middle of muscle sarcomeres. Knocking down leiomodin severely compromised sarcomere assembly in cultured muscle cells, which suggests a role for leiomodin in the nucleation of tropomyosin-decorated filaments in muscles.
authors.affiliation: Boston Biomedical Research Institute, Watertown, MA 02472, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chereau
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Boczkowska
authors.forename: Aneta
authors.initials: A
authors.lastname: Skwarek-Maruszewska
authors.forename: Ikuko
authors.initials: I
authors.lastname: Fujiwara
authors.forename: David B
authors.initials: DB
authors.lastname: Hayes
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rebowski
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Pollard
authors.forename: Roberto
authors.initials: R
authors.lastname: Dominguez
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011817:Rabbits; D051381:Rats; D012518:Sarcomeres / Q000378:metabolism*; D051348:Tropomodulin / Q000737:chemistry; D014335:Tropomyosin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; C528309:LMOD2 protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D051348:Tropomodulin; D014335:Tropomyosin