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MBC in Press, published online ahead of print October 31, 2007
Mol. Biol. Cell 10.1091/mbc.E07-04-0385

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Submitted on April 27, 2007
Revised on October 9, 2007
Accepted on October 22, 2007

Distinct Roles for Two G{alpha}-G{beta} Interfaces in Cell Polarity Control by a Yeast Heterotrimeric G Protein

Shelly C. Strickfaden and Peter M. Pryciak

Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605

Monitoring Editor: Daniel Lew

S. cerevisiae mating pheromones trigger dissociation of a heterotrimeric G protein (G{alpha}{beta}{gamma}) into G{alpha}-GTP and G{beta}{gamma}. The G{beta}{gamma} dimer regulates both 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.


Address correspondence to: Peter M. Pryciak (peter.pryciak{at}umassmed.edu)




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N. A. Lambert
Dissociation of Heterotrimeric G Proteins in Cells
Sci. Signal., June 24, 2008; 1(25): re5 - re5.
[Abstract] [Full Text] [PDF]




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