title: Oligomerization of the diaphanous-related formin FHOD1 requires a coiled-coil motif critical for its cytoskeletal and transcriptional activities.
abstract: The diaphanous-related formin homology 2 domain containing protein 1 (FHOD1) interacts with the Rac GTPase and activates the Rho-ROCK cascade leading to the formation of actin stress fibers. Here, we report the detection of homotypic interactions of FHOD1 in the yeast two-hybrid system, by co-immunoprecipitation and co-localization in mammalian cells. A predicted coiled-coil motif C-terminal to the core FH2 domain, but not the core FH2 domain itself, was critical for self-association of FHOD1. Deletion of both the coiled-coil motif and the core FH2 domain abrogated formation of actin stress fibers and activation of transcription of the serum response element by FHOD1. In contrast, these motifs were dispensable for the physical and functional interaction of FHOD1 with Rac1. Together, these results indicate that oligomerization of FHOD1 via the coiled-coil motif is a critical parameter for its biological activities.
authors.affiliation: Department of Infectious Diseases, Institut Cochin, INSERM U567, CNRS UMR 8104, Université Paris V, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Madrid
authors.forename: Judith E
authors.initials: JE
authors.lastname: Gasteier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bouchet
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schröder
authors.forename: Matthias
authors.initials: M
authors.lastname: Geyer
authors.forename: Serge
authors.initials: S
authors.lastname: Benichou
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Fackler
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D005326:Fetal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D022502:Stress Fibers / Q000378:metabolism / Q000648:ultrastructure*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins; D020830:rac1 GTP-Binding Protein