title: Mammalian formin fhod3 regulates actin assembly and sarcomere organization in striated muscles.
abstract: Actin filament assembly in nonmuscle cells is regulated by the actin polymerization machinery, including the Arp2/3 complex and formins. However, little is known about the regulation of actin assembly in muscle cells, where straight actin filaments are organized into the contractile unit sarcomere. Here, we show that Fhod3, a myocardial formin that localizes to thin actin filaments in a striated pattern, regulates sarcomere organization in cardiomyocytes. RNA interference-mediated depletion of Fhod3 results in a marked reduction in filamentous actin and disruption of the sarcomeric structure. These defects are rescued by expression of wild-type Fhod3 but not by that of mutant proteins carrying amino acid substitution for conserved residues for actin assembly. These findings suggest that actin dynamics regulated by Fhod3 are critical for sarcomere organization in striated muscle cells.
authors.affiliation: Department of Biochemistry, Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Ryu
authors.initials: R
authors.lastname: Takeya
authors.forename: Shiro
authors.initials: S
authors.lastname: Suetsugu
authors.forename: Meikun
authors.initials: M
authors.lastname: Kan-O
authors.forename: Megumi
authors.initials: M
authors.lastname: Narusawa
authors.forename: Akira
authors.initials: A
authors.lastname: Shiose
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tominaga
authors.forename: Hideki
authors.initials: H
authors.lastname: Sumimoto
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; C485994:FHOD3 protein, human; C579478:Fhod3 protein, rat; D000080865:Formins; D008840:Microfilament Proteins; D009124:Muscle Proteins
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