Biomedical subjects

A Nern

Publications and source records attributed to A Nern.

4 recordsLinked to original sources

PubMed2000

Nucleocytoplasmic shuttling of the Cdc42p exchange factor Cdc24p.

Cdc24p, the GDP/GTP exchange factor for the regulator of actin cytoskeleton Cdc42p, localizes to sites of polarized growth. Here we show that Cdc24p shuttles in and out of the yeast nucleus during vegetative growth. Far1p is necessary and sufficient for nuclear accumulation of Cdc24p, suggesting that its nuclear import occurs via an association with Far1p. Nuclear export is triggered either by entry into the cell cycle or by mating pheromone. As Far1p is degraded upon entry into the cell cycle, cell cycle-dependent export of Cdc24p occurs in the absence of Far1p, whereas during mating similar export kinetics indicate that a Cdc24p-Far1p complex is exported. Our results suggest that the nucleus serves as a store of preformed Cdc24p-Far1p complex which is required for chemotropism.

Cell Cycle↗

PubMed2000

G proteins mediate changes in cell shape by stabilizing the axis of polarity.

Upon exposure to mating pheromone, yeast cells change their form to pear-shaped shmoos. We looked at pheromone-dependent cell shape changes in mutants that are unable to orient growth during mating and unable to choose a bud site. In these double mutants, cell surface growth, secretion sites, cytoskeleton, and pheromone receptors are spread out, explaining why these cells are round. In contrast, polarity establishment proteins localize to discrete sites in these mutants. However, the location of these sites wanders. Thus, these mutants are able to initiate polarized growth but fail to maintain the location of growth sites. Our results demonstrate that stabilization of the growth axis requires positional signaling from either the pheromone receptor or specific bud site selection proteins.

Cell Compartmentation↗

PubMed1999

A Cdc24p-Far1p-Gbetagamma protein complex required for yeast orientation during mating.

Oriented cell growth requires the specification of a site for polarized growth and subsequent orientation of the cytoskeleton towards this site. During mating, haploid Saccharomyces cerevisiae cells orient their growth in response to a pheromone gradient overriding an internal landmark for polarized growth, the bud site. This response requires Cdc24p, Far1p, and a heterotrimeric G-protein. Here we show that a two- hybrid interaction between Cdc24p and Gbeta requires Far1p but not pheromone-dependent MAP-kinase signaling, indicating Far1p has a role in regulating the association of Cdc24p and Gbeta. Binding experiments demonstrate that Cdc24p, Far1p, and Gbeta form a complex in which pairwise interactions can occur in the absence of the third protein. Cdc24p localizes to sites of polarized growth suggesting that this complex is localized. In the absence of CDC24-FAR1-mediated chemotropism, a bud site selection protein, Bud1p/Rsr1p, is essential for morphological changes in response to pheromone. These results suggest that formation of a Cdc24p-Far1p-Gbetagamma complex functions as a landmark for orientation of the cytoskeleton during growth towards an external signal.

Amino Acid Sequence↗

PubMed1998

A GTP-exchange factor required for cell orientation.

The Rho-family of GTPases and their regulators are essential for cytoskeletal reorganization and transcriptional activation in response to extracellular signals. Little is known about what links these molecules to membrane receptors. In the budding yeast Saccharomyces cerevisiae, haploid cells respond to mating pheromone through a G-protein-coupled receptor and the betagamma subunit of the G protein, resulting in arrest of the cell cycle, transcriptional activation, and polarized growth towards a mating partner. The Rho-family GTPase Cdc42 and its exchange factor Cdc24 have been implicated in the mating process, but their specific role is unknown. Here we report the identification of cdc24 alleles that do not affect vegetative growth but drastically reduce the ability of yeast cells to mate. When exposed to mating pheromone, these mutants arrest growth, activate transcription, and undergo characteristic morphological and actin-cytoskeleton polarization. However, the mutants are unable to orient towards a pheromone gradient, and instead position their mating projection adjacent to their previous bud site. The mutants are specifically defective in the binding of Cdc24 to the G-protein betagamma subunit. Our results demonstrate that the association of an exchange factor and the betagamma subunit of a hetero-trimeric G protein links receptor-mediated activation to oriented cell growth.

Adaptor Proteins, Signal Transducing↗