The Role of Far1p in Linking the Heterotrimeric G Protein to Polarity Establishment Proteins During Yeast Mating

Abstract

Heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) determine tissue and cell polarity in a variety of organisms. In yeast, cells orient polarized growth toward the mating partner along a pheromone gradient by a mechanism that requires Far1p and Cdc24p. Far1p bound Gbetagamma and interacted with polarity establishment proteins, which organize the actin cytoskeleton. Cells containing mutated Far1p unable to bind Gbetagamma or polarity establishment proteins were defective for orienting growth toward their mating partner. In response to pheromones, Far1p moves from the nucleus to the cytoplasm. Thus, Far1p functions as an adaptor that recruits polarity establishment proteins to the site of extracellular signaling marked by Gbetagamma to polarize assembly of the cytoskeleton in a morphogenetic gradient.

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

“…Therefore, one might not expect FAR1 to play a role in the white cell response, because the role FAR1 plays in the analogous mating process of S. cerevisiae is in the polarization of cells in a gradient of pheromone and G1 arrest (Chang and Herskowitz, 1990;Valtz et al, 1995;Butty et al, 1998). However, in supplemental data to Roberts et al (2000), it was reported that STE12 was not up-regulated by pheromone in a far1⌬ mutant, indicating that Far1p played a role in the up-regulation of pheromone-induced genes.…”

A walk-through of the yeast mating pheromone response pathway

“…As this shape change, or morphogenesis, is in a particular direction, it is polarized, and as the direction chosen is towards the highest concentration of pheromone, it is chemotropic. The Gβ-Far1-Cdc24-Cdc42 branch of the pathway is crucial for the chemotropic polarized morphogenesis that occurs during mating [21,37,[105][106][107]130,140], as are Cdc42 targets such as Bem1, Bni1, Gic1 and Gic2 [20,24,43]. Cells that crawl use similar regulatory strategies [23]; for example, Gβγ-dependent recruitment of a PAK and a Cdc42 exchange factor also occurs in mammalian chemotaxis [89,101].…”

“…A RING-H2 domain in the N-terminal half of Far1 binds to Gβγ; while the C-terminal half of Far1 binds to Cdc24 [21]. Cdc24 is a guanine nucleotide exchange factor (GEF) for Cdc42.…”

“…The thirdGβγ effector is a complex of the Far1 and Cdc24 proteins [21,105]. A RING-H2 domain in the N-terminal half of Far1 binds to Gβγ; while the C-terminal half of Far1 binds to Cdc24 [21].…”

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

“…Far1 mediates the cell cycle arrest in response to pheromone (Peter et al, 1993), and specifies direction of polarized growth during mating by linking the heterotrimeric G bc subunits to the polarity establishment machinery (Butty et al, 1998). The Far1 protein contains a C 3 HC 4 -type ring zinc finger domain with a predicted role in the ubiquitination pathway.…”