Nuclear sequestration of the exchange factor Cdc24 by Far1 regulates cell polarity during yeast mating

Shimada, Yukiko; Gulli, Marie‐Pierre; Peter, Matthias

doi:10.1038/35000073

Cited by 174 publications

(136 citation statements)

References 46 publications

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“…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].…”

Section: G-protein Effectorsmentioning

confidence: 99%

A walk-through of the yeast mating pheromone response pathway

2004

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Section: G-protein Effectorsmentioning

confidence: 99%

A walk-through of the yeast mating pheromone response pathway

2004

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“…However, Net1 regulation is similar to that of CDC24, a GEF for CDC42, in yeast (31,32); CDC24 is imported and kept in the nucleus by association with FAR1. Nuclear export and thus activation of CDC42 are triggered either by entry into the cell cycle, when FAR1 is degraded, or by mating pheromone, which stimulates export of the FAR1⅐CDC24 complex.…”

Section: Discussionmentioning

confidence: 99%

The Rho Exchange Factor Net1 Is Regulated by Nuclear Sequestration

Schmidt¹,

Hall²

2002

Journal of Biological Chemistry

106

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Net1 is a guanine nucleotide exchange factor specific for the small GTPase Rho. Oncogenic activation of Net1 occurs by truncation of the N-terminal part of the protein, which functions as a negative regulatory domain. Here, we have investigated the mechanism of Net1 regulation via its N terminus. We find that Net1 localizes to the nucleus, whereas oncogenic Net1 is found in the cytoplasm. Nuclear import of Net1 is mediated by two nuclear localization signals present in the N terminus of the protein, and forced cytoplasmic localization of Net1 is sufficient to activate Rho. In addition, the pleckstrin homology (PH) domain of Net1 acts as a nuclear export signal. Because an amino acid substitution in the PH domain that inhibits guanine nucleotide exchange factor activity does not inhibit nuclear export, we conclude that this PH domain has at least two functions. Together, our results suggest that Net1 can shuttle in and out of the nucleus, and that activation of Rho by Net1 is controlled by changes in its subcellular localization.

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“…1 Phase-We proposed previously that the Rsr1 GTPase cycle functions to guide proteins necessary for bud formation, such as Cdc24, to the proper bud site (8). It has been recently reported that Cdc24 localizes to the nucleus in early G 1 cells through the association with Far1 and to an incipient bud site in late G 1 phase (13,20,21). However, it is not known how Cdc24 localizes to the incipient bud site in late G 1 phase.…”

Section: K260 -264smentioning

confidence: 99%

“…Yeast strains used in this study are listed in Supplemental Table I. Cdc24-green fluorescent protein (GFP) 1 was expressed using plasmid pYS47 (a gift from M. Peter) (13). YEp13-rsr1 G12V and YEp13-rsr1 K16N were gifts from M. Ruggieri (14).…”

Section: Methodsmentioning

confidence: 99%

Localization of the Rsr1/Bud1 GTPase Involved in Selection of a Proper Growth Site in Yeast

Park¹,

Kang²,

Rachfal³

2002

Journal of Biological Chemistry

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Yeast cells organize their actin cytoskeleton in a highly polarized manner during vegetative growth. The Ras-like GTPase Rsr1/Bud1 and its regulators are required for selection of a specific site for growth. Here we showed that Rsr1/Bud1 was broadly distributed on the plasma membrane and highly concentrated at the incipient bud site and polarized growth sites. We also showed that localization of Cdc24, a guanine nucleotide exchange factor for the Cdc42 GTPase, to the proper bud site was dependent on Rsr1/Bud1. Surprisingly, Rsr1/ Bud1 also localized to intracellular membranes. A mutation in the lysine repeat in the hypervariable region of Rsr1/Bud1 specifically abolished its plasma membrane localization, whereas a mutation at the CAAX motif eliminated both plasma membrane and internal membrane association of Rsr1/Bud1. Thus the lysine repeat and the CAAX motif of Rsr1/Bud1 are important for its localization to the plasma membrane and to the polarized growth sites. This localization of Rsr1/Bud1 is essential for its function in proper bud site selection because both mutations resulted in random bud site selection.Cells of the budding yeast Saccharomyces cerevisiae undergo oriented cell division by selecting a specific site for polarized growth on their cell cortex (1-3). Haploid a and ␣ cells bud in an axial pattern, whereas diploid a/␣ cells bud in a bipolar pattern. The GTPase module consisting of Rsr1/Bud1 (Rsr1 hereafter), its GDP-GTP exchange factor Bud5, and its GTPase-activating protein Bud2 is essential for selecting the proper site for polarized growth in both haploid and diploid cells (4 -7). Based on genetic and biochemical data, we proposed previously that the Rsr1 GTPase module directs bud site assembly to occur at specific locations by recruiting components such as Cdc24 required for bud formation to that site (8). Recruiting these proteins to the presumptive bud site is thought to direct the cytoskeleton and secretory apparatus toward the bud site, thereby restricting new growth to the bud (9). One of the key questions in understanding the molecular basis of cell polarity is how specific sites for actin polymerization are determined.To understand the mechanism of action of the Rsr1 GTPase module, it is crucial to determine whether any of its components are localized to the presumptive bud site. We reported previously that both Bud2 and Bud5 are localized to the presumptive bud site and to discrete sites during the cell cycle (10, 11). This localization is essential for selection of a specific site for growth. Here we report that Rsr1 is broadly distributed on the plasma membrane and is highly concentrated at the incipient bud site and polarized growth sites. Mutational studies indicated that the lysine repeat in the hypervariable region and the CAAX motif of Rsr1 are important for its localization and its role in selection of a proper site for growth. We also show that localization of Cdc24, a guanine nucleotide exchange factor for Cdc42, to the proper bud site is dependent on Rsr1. EXPERIMENTAL PR...

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Nuclear sequestration of the exchange factor Cdc24 by Far1 regulates cell polarity during yeast mating

Cited by 174 publications

References 46 publications

A walk-through of the yeast mating pheromone response pathway

A walk-through of the yeast mating pheromone response pathway

The Rho Exchange Factor Net1 Is Regulated by Nuclear Sequestration

Localization of the Rsr1/Bud1 GTPase Involved in Selection of a Proper Growth Site in Yeast

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