Joshua B Kelley1, Gauri Dixit2, Joshua B Sheetz2, Sai Phanindra Venkatapurapu3, Timothy C Elston4, Henrik G Dohlman5. 1. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 3046 Genetic Medicine Building, Campus Box 7260, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 4009 Genetic Medicine Building, Campus Box 7365, Chapel Hill, NC 27599, USA. 2. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 3046 Genetic Medicine Building, Campus Box 7260, Chapel Hill, NC 27599, USA. 3. Department of Pharmacology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 4009 Genetic Medicine Building, Campus Box 7365, Chapel Hill, NC 27599, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 4092 Genetic Medicine Building, Campus Box 7365, Chapel Hill, NC 27599, USA. 4. Department of Pharmacology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 4009 Genetic Medicine Building, Campus Box 7365, Chapel Hill, NC 27599, USA. Electronic address: timothy_elston@med.unc.edu. 5. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 3046 Genetic Medicine Building, Campus Box 7260, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 4009 Genetic Medicine Building, Campus Box 7365, Chapel Hill, NC 27599, USA. Electronic address: henrik_dohlman@med.unc.edu.
Abstract
BACKGROUND: Septins are well known to form a boundary between mother and daughter cells in mitosis, but their role in other morphogenic states is poorly understood. RESULTS: Using microfluidics and live-cell microscopy, coupled with new computational methods for image analysis, we investigated septin function during pheromone-dependent chemotropic growth in yeast. We show that septins colocalize with the regulator of G protein signaling (RGS) Sst2, a GTPase-activating protein that dampens pheromone receptor signaling. We show further that the septin structure surrounds the polar cap, ensuring that cell growth is directed toward the source of pheromone. When RGS activity is abrogated, septins are partially disorganized. Under these circumstances, the polar cap travels toward septin structures and away from sites of exocytosis, resulting in a loss of gradient tracking. CONCLUSIONS: Septin organization is dependent on RGS protein activity. When assembled correctly, septins promote turning of the polar cap and proper tracking of a pheromone gradient.
BACKGROUND: Septins are well known to form a boundary between mother and daughter cells in mitosis, but their role in other morphogenic states is poorly understood. RESULTS: Using microfluidics and live-cell microscopy, coupled with new computational methods for image analysis, we investigated septin function during pheromone-dependent chemotropic growth in yeast. We show that septins colocalize with the regulator of G protein signaling (RGS) Sst2, a GTPase-activating protein that dampens pheromone receptor signaling. We show further that the septin structure surrounds the polar cap, ensuring that cell growth is directed toward the source of pheromone. When RGS activity is abrogated, septins are partially disorganized. Under these circumstances, the polar cap travels toward septin structures and away from sites of exocytosis, resulting in a loss of gradient tracking. CONCLUSIONS: Septin organization is dependent on RGS protein activity. When assembled correctly, septins promote turning of the polar cap and proper tracking of a pheromone gradient.
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