title: Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating.
abstract: Cell pairing is central for many processes, including immune defense, neuronal connection, hyphal fusion, and sexual reproduction. How does a cell orient toward a partner, especially when faced with multiple choices? Fission yeast Schizosaccharomyces pombe P and M cells, which respectively express P and M factor pheromones [1, 2], pair during the mating process induced by nitrogen starvation. Engagement of pheromone receptors Map3 and Mam2 [3, 4] with their cognate pheromone ligands leads to activation of the Gα protein Gpa1 to signal sexual differentiation [3, 5, 6]. Prior to cell pairing, the Cdc42 GTPase, a central regulator of cell polarization, forms dynamic zones of activity at the cell periphery at distinct locations over time [7]. Here we show that Cdc42-GTP polarization sites contain the M factor transporter Mam1, the general secretion machinery, which underlies P factor secretion, and Gpa1, suggesting that these are sub-cellular zones of pheromone secretion and signaling. Zone lifetimes scale with pheromone concentration. Computational simulations of pair formation through a fluctuating zone show that the combination of local pheromone release and sensing, short pheromone decay length, and pheromone-dependent zone stabilization leads to efficient pair formation. Consistently, pairing efficiency is reduced in the absence of the P factor protease. Similarly, zone stabilization at reduced pheromone levels, which occurs in the absence of the predicted GTPase-activating protein for Ras, leads to reduction in pairing efficiency. We propose that efficient cell pairing relies on fluctuating local signal emission and perception, which become locked into place through stimulation.
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Merlini
authors.affiliation: Department of Physics, Lehigh University, Bethlehem, PA 18015, USA.
authors.forename: Bita
authors.initials: B
authors.lastname: Khalili
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland.
authors.forename: Felipe O
authors.initials: FO
authors.lastname: Bendezú
authors.affiliation: Department of Physics, Lehigh University, Bethlehem, PA 18015, USA; Department of Physics, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hurwitz
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vincenzetti
authors.affiliation: Department of Physics, Lehigh University, Bethlehem, PA 18015, USA. Electronic address: vavylonis@lehigh.edu.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vavylonis
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland. Electronic address: sophie.martin@unil.ch.
authors.forename: Sophie G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D002459:Cell Fusion; D016764:Cell Polarity; D010675:Pheromones / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D010675:Pheromones; D029702:Schizosaccharomyces pombe Proteins; C107004:mam1 protein, S pombe; D020764:cdc42 GTP-Binding Protein