Ras; Cdc42; Cell fusion; Fission yeast schizosaccharomyces pombe; Cell polarization; Pheromone
Vještica Aleksandar, Merlini Laura, Nkosi Pedro Junior, Martin Sophie G. (2018), Gamete fusion triggers bipartite transcription factor assembly to block re-fertilization, in Nature
, 560(7718), 397-400.
Khalili Bita, Merlini Laura, Vincenzetti Vincent, Martin Sophie G., Vavylonis Dimitrios (2018), Exploration and stabilization of Ras1 mating zone: A mechanism with positive and negative feedbacks, in PLOS Computational Biology
, 14(7), e1006317-e1006317.
Merlini Laura, Khalili Bita, Dudin Omaya, Michon Laetitia, Vincenzetti Vincent, Martin Sophie G (2018), Inhibition of Ras activity coordinates cell fusion with cell-cell contact during yeast mating, in J Cell Biol
, 217, 1467.
Dudin Omaya, Merlini Laura, Bendezu Felipe, Groux Raphael, Vincenzetti Vincent, Martin Sophie G (2017), A systematic screen for morphological abnormalities during fission yeast sexual reproduction identifies a mechanism of actin aster formation for cell fusion, in PLoS Genet
, 13, e1006721.
Merlini Laura, Vjestica Aleksandar, Dudin Omaya, Bendezu Felipe, Martin Sophie G (2017), Live Cell Imaging of the Schizosaccharomyces pombe Sexual Life Cycle, in Hagan Iain M, Carr Antony M, Grallert Agnes , Nurse Paul (ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 795.
Merlini Laura, Khalili Bita, Bendezu Felipe, Hurwitz Daniel, Vavylonis Dimitrios, Martin Sophie G (2017), Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating, in Current Biology
, 26, 1117.
Vjestica Aleksandar, Merlini Laura, Dudin Omaya, Bendezu Felipe, Martin Sophie G (2016), Microscopy of Fission Yeast Sexual Lifecycle, in J Vis Exp
, 109, -.
Martin Sophie G (2016), Role and organization of the actin cytoskeleton during cell-cell fusion, in Semin Cell Dev Biol
, 60, 121.
Dudin Omaya, Merlini Laura, Martin Sophie G (2016), Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion, in Genes and Development
, 30, 2226.
Martin Sophie G (2015), Spontaneous cell polarization: Feedback control of Cdc42 GTPase breaks cellular symmetry, in Bioessays
Cells are highly spatially organized, through mechanisms that are conceptually and molecularly very conserved. One can define three steps for cell polarization. First, landmarks positioned in response to intrinsic or extracellular signals mark a cortical site. Second, small G proteins of the Rho/Ras family, such as Cdc42, become locally activated. Third, these recruit effectors and activate signaling pathways to transduce this spatial information into productive cell organization. In this series of events, the Cdc42 module is constantly re-used, not only in response to distinct landmarks, but also to produce distinct polarization outcomes. How are distinct polarity states achieved and regulated? The unicellular yeast models have been instrumental in deciphering the mechanisms of cell polarization and establishing these basic concepts. We have recently described that mating fission yeast cells sequentially exhibit distinct polarization states: at low pheromone levels, cells first display an exploratory state, where the polarization machinery appears active, but fails to recruits cell wall enzymes for polarized growth; at higher pheromone levels, cells then show a polarized growth state as they extend a projection towards a mate; finally, the effective polarization shifts to the organization of a cell-cell fusion machinery for zygote formation. This proposal asks how transition through these states is controlled and how the cell-cell fusion machinery is eventually assembled. There are two specific aims: Aim 1: Role of Ras GTPase in regulating pheromone-dependent polarization statesHow pheromone perception is transduced into spatial cellular organization is unclear, but the sole fission yeast Ras GTPase likely play a central role, as it is required for both signal transduction and cell polarization. Further, deletion of the Ras1 negative regulator, its GTPase Activating Protein Gap1, enhances the cell polarization response in low levels of pheromone, suggesting that Ras1 activity levels modulate the polarization response. We will define the molecular mechanisms by which Ras1 becomes activated at sites of pheromone perception, as well as the mechanisms by which pheromone signaling modulates Ras1 activity. We will also strive to separate the functions of Ras1 in signaling from its spatial role in cell polarization, and investigate where it acts. Our work will define the mechanisms by which a graded external signal is converted to a binary spatial cell response. This is a general cellular problem and the molecular players involved are highly conserved (GPCR signaling machinery, RAS and its regulators). The concepts we will uncover are thus likely to be valid beyond the yeast model. Aim 2: Hierarchical description of the cell-cell fusion machineryCell-cell fusion mechanisms are poorly understood in most organisms. We have conducted a systematic screen for mutants defective in the mating process, which identified many fusion mutants, and described several steps in the fusion process. Our aim is to establish a hierarchical description of the parts list for cell-cell fusion, and set up correlative EM-fluorescence microscopy to describe the fusion process. By initiating a systematic study of cell-cell fusion in fission yeast, using the vast array of genetic and cell biological tools available, we aim to provide a model in which a global systems-level understanding can eventually be achieved.