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The mating of budding yeast depends on chemotropism, a fundamental cellular process. Haploid yeast cells of opposite mating type signal their positions to one another through mating pheromones. We have proposed a deterministic gradient sensing model that explains how these cells orient toward their mating partners. Using the cell-cycle determined default polarity site (DS), cells assemble a gradient tracking machine (GTM) composed of signaling, polarity, and trafficking proteins. After assembly, the GTM redistributes up the gradient, aligns with the pheromone source, and triggers polarized growth toward the partner. Since positive feedback mechanisms drive polarized growth at the DS, it is unclear how the GTM is released for tracking. What prevents the GTM from triggering polarized growth at the DS? Here, we describe two mechanisms that are essential for tracking: inactivation of the Ras GTPase Bud1 and positioning of actin-independent vesicle delivery upgradient.
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Mating yeast cells use an intrinsic polarity site to assemble a pheromone-gradient tracking machine
The mating of budding yeast depends on chemotropism, a fundamental cellular process. The two yeast mating types secrete peptide pheromones that bind to GPCRs on cells of the opposite type. Cells find and contact a partner by determining the direction of the pheromone source and polarizing their growth toward it. Actin-directed secretion to the chemotropic growth site (CS) generates a mating projection. When pheromone-stimulated cells are unable to sense a gradient, they form mating projections where they would have budded in the next cell cycle, at a position called the default polarity site (DS). Numerous models have been proposed to explain yeast gradient sensing, but none address how cells reliably switch from the intrinsically determined DS to the gradient-aligned CS, despite a weak spatial signal. Here we demonstrate that, in mating cells, the initially uniform receptor and G protein first polarize to the DS, then redistribute along the plasma membrane until they reach the CS. Our data indicate that signaling, polarity, and trafficking proteins localize to the DS during assembly of what we call the gradient tracking machine (GTM). Differential activation of the receptor triggers feedback mechanisms that bias exocytosis upgradient and endocytosis downgradient, thus enabling redistribution of the GTM toward the pheromone source. The GTM stabilizes when the receptor peak centers at the CS and the endocytic machinery surrounds it. A computational model simulates GTM tracking and stabilization and correctly predicts that its assembly at a single site contributes to mating fidelity.
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- Award ID(s):
- 1818067
- PAR ID:
- 10126933
- Publisher / Repository:
- DOI PREFIX: 10.1083
- Date Published:
- Journal Name:
- Journal of Cell Biology
- Volume:
- 218
- Issue:
- 11
- ISSN:
- 0021-9525
- Page Range / eLocation ID:
- p. 3730-3752
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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