Mammalian formin fhod3 regulates actin assembly and sarcomere organization in striated muscles.
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.
Taniguchi
Kenichiro
K
Department of Biochemistry, Graduate School of Medical Sciences, Fukuoka, Japan.
Takeya
Ryu
R
Suetsugu
Shiro
S
Kan-O
Meikun
M
Narusawa
Megumi
M
Shiose
Akira
A
Tominaga
Ryuji
R
Sumimoto
Hideki
H
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*
D000199:Actins; C485994:FHOD3 protein, human; C579478:Fhod3 protein, rat; D000080865:Formins; D008840:Microfilament Proteins; D009124:Muscle Proteins
Curr Opin Cell Biol. 2006 Feb;18(1):11-7
16364624
Circ Res. 1985 Jun;56(6):884-94
2988814
J Muscle Res Cell Motil. 2005;26(6-8):343-54
16465476
J Mol Cell Cardiol. 1973 Aug;5(4):341-50
4355337
Dev Cell. 2007 Dec;13(6):828-42
18061565
Annu Rev Biophys Biomol Struct. 2007;36:451-77
17477841
J Cell Sci. 2003 Nov 15;116(Pt 22):4567-75
14576350
J Biol Chem. 2001 Aug 31;276(35):33175-80
11432863
Nature. 1995 Sep 7;377(6544):83-6
7544875
Semin Cell Dev Biol. 2008 Dec;19(6):511-9
18793739
J Biol Chem. 2004 May 7;279(19):20076-87
14990563
J Cell Biol. 1995 Jan;128(1-2):61-70
7822423
Cell. 1999 Jul 23;98(2):159-69
10428028
Genes Cells. 2005 Jul;10(7):665-78
15966898
Cell. 2004 Oct 29;119(3):419-29
15507212
Annu Rev Cell Dev Biol. 2002;18:637-706
12142273
Anal Biochem. 1980 Apr;103(2):316-22
6892979
Science. 2008 Apr 11;320(5873):239-43
18403713
Mol Biol Cell. 2002 Nov;13(11):4088-99
12429848
J Cell Biol. 2003 Jun 9;161(5):875-87
12796476
Trends Cell Biol. 2000 Sep;10(9):355-62
10932092
Nat Cell Biol. 2001 Jun;3(6):544-51
11389438
Mol Biol Cell. 2009 Apr;20(8):2160-73
19244341
Nature. 2005 Feb 3;433(7025):488-94
15635372
Circulation. 2003 Mar 18;107(10):1418-23
12642364
Annu Rev Biochem. 2007;76:593-627
17373907
Nat Cell Biol. 2007 Oct;9(10):1110-21
17909522
Proc Natl Acad Sci U S A. 1972 Feb;69(2):308-12
4501115
Cell. 2004 Mar 5;116(5):711-23
15006353
J Biol Chem. 2001 Dec 7;276(49):46453-9
11590143
J Cell Biol. 1984 Feb;98(2):518-24
6537951
Curr Biol. 2003 Oct 14;13(20):1820-3
14561409