| Title: | A positive feedback loop involving the Spa2 SHD domain contributes to focal polarization |
| Author(s): | Lawson MJ; Drawert B; Petzold L; Yi TM; |
| Address: | "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, United States of America. Department of Computer Science, University of North Carolina Asheville, Asheville, NC, United States of America. Department of Computer Science, University of California, Santa Barbara, Santa Barbara, CA, United States of America. Molecular, Cellular, and Developmental Biology, 3131 Biological Sciences II, University of California, Santa Barbara, Santa Barbara, CA, United States of America" |
| DOI: | 10.1371/journal.pone.0263347 |
| ISSN/ISBN: | 1932-6203 (Electronic) 1932-6203 (Linking) |
| Abstract: | "Focal polarization is necessary for finely arranged cell-cell interactions. The yeast mating projection, with its punctate polarisome, is a good model system for this process. We explored the critical role of the polarisome scaffold protein Spa2 during yeast mating with a hypothesis motivated by mathematical modeling and tested by in vivo experiments. Our simulations predicted that two positive feedback loops generate focal polarization, including a novel feedback pathway involving the N-terminal domain of Spa2. We characterized the latter using loss-of-function and gain-of-function mutants. The N-terminal region contains a Spa2 Homology Domain (SHD) which is conserved from yeast to humans, and when mutated largely reproduced the spa2Delta phenotype. Our work together with published data show that the SHD domain recruits Msb3/4 that stimulates Sec4-mediated transport of Bud6 to the polarisome. There, Bud6 activates Bni1-catalyzed actin cable formation, recruiting more Spa2 and completing the positive feedback loop. We demonstrate that disrupting this loop at any point results in morphological defects. Gain-of-function perturbations partially restored focal polarization in a spa2 loss-of-function mutant without restoring localization of upstream components, thus supporting the pathway order. Thus, we have collected data consistent with a novel positive feedback loop that contributes to focal polarization during pheromone-induced polarization in yeast" |
| Keywords: | Actins/metabolism Cell Communication/*physiology Cell Polarity/genetics/*physiology Cytoskeletal Proteins/genetics/*metabolism/physiology Feedback GTPase-Activating Proteins/metabolism Microfilament Proteins/metabolism Saccharomyces cerevisiae/genetics/me; |
| Notes: | "MedlineLawson, Michael J Drawert, Brian Petzold, Linda Yi, Tau-Mu eng R01 EB014877/EB/NIBIB NIH HHS/ R01 GM113241/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. 2022/02/09 PLoS One. 2022 Feb 8; 17(2):e0263347. doi: 10.1371/journal.pone.0263347. eCollection 2022" |
