Regulation of a Differentiation MAPK Pathway by a Novel Integrated Signaling Network and Multiple Sensors
Caccamise, Lauren M.
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Filamentous growth is a cell differentiation program utilized by Saccharomyces cerevisiae to respond to nutrient limitation in the environment. This process is principally controlled by a mitogen-activated protein kinase (MAPK) pathway but is also impacted by a number of other pathways including Ras2p-cAMP-PKA, Target of Rapamycin, Rim101, and mitochondrial retrograde. Using a high-throughput genetic screening approach in conjunction with directed gene-deletion analysis, I have identified 97 new regulators of the filamentous growth MAPK pathway. These new regulators created new connections to the filamentous growth MAPK pathway as well as extended previously known connections. I have linked several of the pathways governing filamentous growth together as part of an integrated signaling network by showing that these pathways regulate each other's transcriptional targets. This network indicates an intricate level of communication and coordination among these pathways that has not been previously appreciated. I show that proper coordination of the filamentous growth MAPK pathway is essential for proper morphogenesis and this is a potential reason for the many inputs used to control this response. The filamentous growth MAPK pathway is also regulated by three transmembrane proteins - Msb2p, Sho1p, and Opy2p. Here these three proteins are compared to determine that they have specific functions in regulating filamentous growth. The three proteins exhibit different localization patterns and rates of turnover from the plasma membrane. I show that the Rim101 pathway affects the filamentous growth MAPK pathway independently of the ESCRT pathway which shares components with the Rim101 pathway. Additionally, I have shown that overexpression of the arrestin protein Aly1p results in mislocalized Msb2p and diminished pathway activity.