Distinct roles for two G alpha-G beta interfaces in cell polarity control by a yeast heterotrimeric G protein

作者：Strickfaden Shelly C; Pryciak Peter M^*

来源：Molecular Biology of the Cell, 2008, 19(1): 181-197.

DOI：10.1091/mbc.E07-04-0385

Saccharomyces cerevisiae mating pheromones trigger dissociation of a heterotrimeric G protein (G alpha beta gamma) into G alpha-guanosine triphosphate (GTP) and G beta gamma. The G beta gamma dimer regulates both mitogen-activated protein (MAP) kinase cascade signaling and cell polarization. Here, by independently activating the MAP kinase pathway, we studied the polarity role of G beta gamma in isolation from its signaling role. MAP kinase signaling alone could induce cell asymmetry but not directional growth. Surprisingly, active G beta gamma, either alone or with G alpha-GTP, could not organize a persistent polarization axis. Instead, following pheromone gradients (chemotropism) or directional growth without pheromone gradients (de novo polarization) required an intact receptor-G alpha beta gamma module and GTP hydrolysis by G alpha. Our results indicate that chemoattractant-induced cell polarization requires continuous receptor-G alpha beta gamma communication but not modulation of MAP kinase signaling. To explore regulation of G beta gamma by G alpha, we mutated G beta residues in two structurally distinct G alpha-G beta binding interfaces. Polarity control was disrupted only by mutations in the N-terminal interface, and not the Switch interface. Incorporation of these mutations into a G beta-G alpha fusion protein, which enforces subunit proximity, revealed that Switch interface dissociation regulates signaling, whereas the N-terminal interface may govern receptor-G alpha beta gamma coupling. These findings raise the possibility that the G alpha beta gamma heterotrimer can function in a partially dissociated state, tethered by the N-terminal interface.

• 出版日期2008-1