title: FHOD1 coordinates actin filament and microtubule alignment to mediate cell elongation.
abstract: Diaphanous-related formins (DRFs) are actin nucleators that mediate rearrangements of the actin cytoskeleton downstream of specific Rho GTPases. The DRF Formin Homology 2 Domain containing 1 (FHOD1) interacts with the Rac1 GTPase and induces the formation of and associates with bundled actin stress fibers. Here we report that active FHOD1 also coordinates microtubules with these actin stress fibers. Expression of a constitutive active FHOD1 variant in HeLa cells not only resulted in pronounced formation of FHOD1-actin fibers but also caused marked cell elongation and parallel alignment of microtubules without affecting cytokinesis of these cells. The analysis of deletions in the FH1 and FH2 functional regions revealed that the integrity of both domains was strictly required for FHOD1's effects on the cytoskeleton. Dominant-negative approaches demonstrated that filament coordination and cell elongation depended on the activity of the Rho-ROCK cascade, but did not involve Rac or Cdc42 activity. Experimental depolymerization of actin filaments or microtubules revealed that the formation of FHOD1-actin fibers was a prerequisite for the polarization of microtubules. However, only simultaneous disruption of both filament systems reversed the cell elongation induced by activated FHOD1. Thus, sustained cell elongation was a consequence of FHOD1-mediated actin-microtubule coordination. These results suggest filament coordination as a conserved function of mammalian DRFs.
authors.affiliation: Abteilung Virologie, Universitätsklinikum Heidelberg, INF 324, D-69120 Heidelberg, Germany.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Gasteier
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schroeder
authors.forename: Walter
authors.initials: W
authors.lastname: Muranyi
authors.forename: Ricardo
authors.initials: R
authors.lastname: Madrid
authors.forename: Serge
authors.initials: S
authors.lastname: Benichou
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Fackler
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D048749:Cytokinesis / Q000187:drug effects; D005326:Fetal Proteins / Q000235:genetics / Q000502:physiology*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000502:physiology
chemical_list: C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins; D015638:Cytochalasin D; D020741:rho GTP-Binding Proteins; D015739:Nocodazole