title: Biochemical Activities of the Wiskott-Aldrich Syndrome Homology Region 2 Domains of Sarcomere Length Short (SALS) Protein.
abstract: Drosophila melanogaster sarcomere length short (SALS) is a recently identified Wiskott-Aldrich syndrome protein homology 2 (WH2) domain protein involved in skeletal muscle thin filament regulation. SALS was shown to be important for the establishment of the proper length and organization of sarcomeric actin filaments. Here, we present the first detailed characterization of the biochemical activities of the tandem WH2 domains of SALS (SALS-WH2). Our results revealed that SALS-WH2 binds both monomeric and filamentous actin and shifts the monomer-filament equilibrium toward the monomeric actin. In addition, SALS-WH2 can bind to but fails to depolymerize phalloidin- or jasplakinolide-bound actin filaments. These interactions endow SALS-WH2 with the following two major activities in the regulation of actin dynamics: SALS-WH2 sequesters actin monomers into non-polymerizable complexes and enhances actin filament disassembly by severing, which is modulated by tropomyosin. We also show that profilin does not influence the activities of the WH2 domains of SALS in actin dynamics. In conclusion, the tandem WH2 domains of SALS are multifunctional regulators of actin dynamics. Our findings suggest that the activities of the WH2 domains do not reconstitute the presumed biological function of the full-length protein. Consequently, the interactions of the WH2 domains of SALS with actin must be tuned in the cellular context by other modules of the protein and/or sarcomeric components for its proper functioning.
authors.affiliation: From the Department of Biophysics, University of Pécs Medical School, Szigeti Str. 12, Pécs H-7624.
authors.forename: Mónika Ágnes
authors.initials: MÁ
authors.lastname: Tóth
authors.affiliation: From the Department of Biophysics, University of Pécs Medical School, Szigeti Str. 12, Pécs H-7624.
authors.forename: Andrea Kinga
authors.initials: AK
authors.lastname: Majoros
authors.affiliation: From the Department of Biophysics, University of Pécs Medical School, Szigeti Str. 12, Pécs H-7624.
authors.forename: Andrea Teréz
authors.initials: AT
authors.lastname: Vig
authors.affiliation: the Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726.
authors.forename: Ede
authors.initials: E
authors.lastname: Migh
authors.affiliation: From the Department of Biophysics, University of Pécs Medical School, Szigeti Str. 12, Pécs H-7624, the Szentágothai Research Center, Ifjúság Str. 34, H-7624 Pécs, and the Nuclear-Mitochondrial Interactions Research Group and the Office for Subsidized Research Units.
authors.forename: Miklós
authors.initials: M
authors.lastname: Nyitrai
authors.affiliation: the Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungarian Academy of Sciences-University of Pécs, Nádor u. 7, H-1051 Budapest, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Mihály
authors.affiliation: From the Department of Biophysics, University of Pécs Medical School, Szigeti Str. 12, Pécs H-7624, the Szentágothai Research Center, Ifjúság Str. 34, H-7624 Pécs, and beata.bugyi@aok.pte.hu.
authors.forename: Beáta
authors.initials: B
authors.lastname: Bugyi
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D058105:Polymerization; D051304:Profilins / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014335:Tropomyosin / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D051304:Profilins; C525781:SALS protein, Drosophila; D014335:Tropomyosin; D011392:Proline
keywords: Drosophila; WH2 domain; actin; intrinsically disordered protein; multifunctional protein; sarcomere; sequestration; severing; skeletal muscle