Supplement Request: The Role of Anillins in Gradient Tracking

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Project Summary - No updates from original submission GPCR signaling drives cell polarization in the yeast pheromone response. In response to pheromone, cells polarize their cytoskeleton and make a mating projection to fuse with a mating partner. At the base of these mating projections are septin structures, serving to anchor signaling proteins and promote membrane curvature. Septins are also important for mitosis where they play a key role in cytokinesis. Anillins are conserved signaling proteins responsible for coordinating the septin cytoskeleton with microtubules, actin, and Rho signaling during cytokinesis. In this proposal, we seek to characterize the role of the anillins Boi1 and BOi2 in regulating septins during the pheromone response. We hypothesize that this contributes to polarized growth and that the anillins signal through regulation of the PP1 phosphatase. In Aim 1, we will examine what signaling events lie upstream of anillin function during the pheromone response. We will use live cell microscopy in microfluidic devices, computational image analysis and yeast genetics to test the role of different anillin domains in controlling the localization of the anillins during the pheromone response. In Aim 2, we will examine the downstream effects of anillin function in the pheromone response. Using the same technical approaches as in Aim 1, we will test the effect of anillins perturbation (mutations and deletions) on downstream polarity signaling, septin dynamics, gradient tracking, and mating. We anticipate that we will discover a non-mitotic role for anillins in the regulation of the septin cytoskeleton. The signaling networks we are studying are conserved from yeast to humans, where anillins are expressed in neurons and overexpressed in cancer. Thus, these studies will enhance our understanding of anillin and septin roles in human health.