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oai:docta.ucm.es:20.500.14352/976012025-08-29T14:36:19Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Gasteier, Judith author Schroeder, Sebastian author Muranyi, Walter author Madrid González, Ricardo author Benichou, Serge author Fackler, Oliver 2024-02-01T11:33:35Z 2024-02-01T11:33:35Z 2005 Gasteier, Judith E., et al. «FHOD1 Coordinates Actin Filament and Microtubule Alignment to Mediate Cell Elongation». Experimental Cell Research, vol. 306, n.o 1, mayo de 2005, pp. 192-202. https://doi.org/10.1016/j.yexcr.2005.02.006. 0014-4827 10.1016/j.yexcr.2005.02.006 https://hdl.handle.net/20.500.14352/97601 https://doi.org/10.1016/j.yexcr.2005.02.006 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. eng Attribution-NonCommercial-NoDerivatives 4.0 International FHOD1 coordinates actin filament and microtubule alignment to mediate cell elongation journal article 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URL https://docta.ucm.es/bitstreams/78b1c252-3f0f-4fd9-9ce4-aa5fe7329e84/download File MD5 093bd3d4e35a49af8faeeb8dda86f407 4066863 application/pdf Cell_elongation_mediation.pdf