The guanine nucleotide exchange factor RasGRF1 directly binds microtubules via DHPH2-mediated interaction

The FEBS Journal
Greta ForlaniRenata Zippel

Abstract

RasGRF is a family of guanine nucleotide exchange factors with dual specificity for both Ras and Rac GTPases. In this study, using mouse brain extracts, we show that both RasGRF1 and RasGRF2 interact with microtubules in an in vitro microtubule assembly system and this binding is very tight. To characterize this association, recombinant purified proteins containing different regions of RasGRF1 were tested for their ability to bind microtubules preassembled from pure tubulin. Only the DHPH2 tandem directly associates with microtubules, whereas the isolated DH or PH2 domains do not, indicating that the entire DHPH2 region is required for this association. The interaction occurs with high affinity (Kd approximately = 2 microM) and with a stoichiometry, at saturating conditions, of one DHPH2 molecule for two tubulin dimers. Competition experiments support the hypothesis that the DHPH2 module is largely responsible for RasGRF1-microtubule interaction. In vivo colocalization of RasGRF1 and microtubules was also observed by fluorescence confocal microscopy in nonneuronal cells after stimulation with an oxidative stress agent and in highly differentiated neuron-like cells. Identification of microtubules as new binding partners of RasGR...Continue Reading

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Citations

Jul 9, 2008·Journal of Molecular Neuroscience : MN·Paola LavagniRenata Zippel
Aug 31, 2011·Journal of Biomolecular Screening·Balajee R SomalingaPhilip J Thomas
Sep 17, 2008·BMC Biochemistry·Konstantin G ChernovPatrick A Curmi
Jul 4, 2012·International Journal of Oncology·Maciej TarnowskiMagda Kucia
Jun 11, 2008·Biochimica Et Biophysica Acta·László Buday, Julian Downward
Nov 30, 2010·Biochimica Et Biophysica Acta·Alberto Fernández-Medarde, Eugenio Santos

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