G protein activation is prerequisite for functional coupling between Gα/Gβγ and tubulin/microtubules

Heterotrimeric G proteins participate in signal transduction by transferring signals from cell surface receptors to intracellular effector molecules. Interestingly, recent results suggest that G proteins also interact with microtubules and participate in cell division and differentiation. It has been shown earlier that both α and βγ subunits of G proteins modulate microtubule assembly in vitro. Since G protein activation and subsequent dissociation of α and βγ subunits are necessary for G proteins to participate in signaling processes, here we asked if similar activation is required for modulation of microtubule assembly by G proteins. We reconstituted Gαβγ heterotrimer from myristoylated-Gα and prenylated-Gβγ, and found that the heterotrimer blocks Gi1α activation of tubulin GTPase and inhibits the ability of Gβ1γ2 to promote in vitro microtubule assembly. Results suggest that G protein activation is required for functional coupling between Gα/Gβγ and tubulin/microtubules, and supports the notion that regulation of microtubules is an integral component of G protein mediated signaling.