title: TheDrosophilaformin Fhos is a primary mediator of sarcomeric thin-filament array assembly.
abstract: Actin-based thin filament arrays constitute a fundamental core component of muscle sarcomeres. We have used formation of theDrosophilaindirect flight musculature for studying the assembly and maturation of thin-filament arrays in a skeletal muscle model system. Employing GFP-tagged actin monomer incorporation, we identify several distinct phases in the dynamic construction of thin-filament arrays. This sequence includes assembly of nascent arrays after an initial period of intensive microfilament synthesis, followed by array elongation, primarily from filament pointed-ends, radial growth of the arrays via recruitment of peripheral filaments and continuous barbed-end turnover. Using genetic approaches we have identified Fhos, the singleDrosophilahomolog of the FHOD sub-family of formins, as a primary and versatile mediator of IFM thin-filament organization. Localization of Fhos to the barbed-ends of the arrays, achieved via a novel N-terminal domain, appears to be a critical aspect of its sarcomeric roles.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Arkadi
authors.initials: A
authors.lastname: Shwartz
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Nagaraju
authors.initials: N
authors.lastname: Dhanyasi
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eyal D
authors.initials: ED
authors.lastname: Schejter
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ben-Zion
authors.identifier: 0000-0003-4903-8889
authors.initials: BZ
authors.lastname: Shilo
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D000080865:Formins; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D046911:Macromolecular Substances / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D012518:Sarcomeres / Q000378:metabolism*
chemical_list: D000199:Actins; D029721:Drosophila Proteins; C000591106:Fhos protein, Drosophila; D000080865:Formins; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins
keywords: D. melanogaster; Fhos/FHOD; cell biology; developmental biology; formin; muscle actin; muscle fiber; sarcomere; stem cells