Regulation of cell morphogenesis by targeted noise suppression and trafficking of a G protein alpha subunit

Regulation of cell morphogenesis by targeted noise suppression and trafficking of a G protein alpha subunit Public Deposited

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Creator

Dixit, Gauri
- Affiliation: School of Medicine, Department of Biochemistry and Biophysics

Abstract

G proteins and their associated receptors form the largest class of proteins that receive and transduce chemical and sensory signals. Regulation of G proteins therefore, is critical to appropriate cellular responses. The work in this thesis evaluates a new function for a known regulator of signaling and identifies a new class of previously unknown regulators that mediate G protein trafficking. Using a yeast model system we demonstrate a novel role for the Regulator of G protein Signaling (RGS) protein in suppression of cell-to-cell variability. Furthermore we identify a novel cascade of ubiquitin-binding domain (UBDs) proteins that serve to deliver the Gα protein from the plasma membrane to the vacuole. Through biochemical assays and single cell analysis we find that the RGS and UBD proteins regulate cellular morphogenesis during signaling. More broadly through this work we were able to uncouple signal and noise in a prototypical stimulus-response pathway and demonstrate for the first time the consequences of G protein trafficking in a non-visual system. This work is important because a thorough understanding of how G protein signaling is spatially and temporally regulated will eventually lead to new drug targets, and more effective or targeted therapeutics.

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