Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation.
Formins constitute a family of eukaryotic proteins that are considered to function as a cytoskeleton organizer to regulate morphogenesis, cell polarity and cytokinesis. Fhos is a recently identified mammalian formin, which contains the conserved domains FH (formin homology) 1 and FH2 in the middle region and the Dia-autoregulatory domain (DAD) in the C-terminus. The role of Fhos in the regulation of cytoskeleton, however, has remained unknown. Here we show that Fhos, in an active form, induces the formation of actin stress fibers and localizes to the actin-based structure. Fhos appears to normally exist in a closed inactive form via an intramolecular interaction between the N-terminal region and the C-terminal DAD. Both FH1 and FH2 domains are required for the induction of the stress fiber formation. However, the N-terminal region of Fhos is required for the targeting of this protein to stress fibers, which is probably mediated via its F-actin-binding activity. We also show that Fhos occurs as a homotypic complex in cells. The self-association of Fhos seems to be mediated via the FH2 domain: the domains bind to each other in a direct manner. Thus, the mammalian formin Fhos, which directly binds to F-actin via the N-terminal region, forms a homotypic complex via the FH2 domain to organize actin cytoskeleton.
Takeya
Ryu
R
Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Sumimoto
Hideki
H
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism*; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011483:Proteidae; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D022502:Stress Fibers / Q000378:metabolism*
D000199:Actins; C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins