Access Type

Open Access Dissertation

Date of Award

January 2011

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Pharmacology

First Advisor

Nicholas G. Davis

Abstract

Palmitoylation is a post-translational lipid modification that allows proteins to interact with membranes. In the yeast Saccharomyces cerevisiae, the casein kinase Yck2 is palmitoylated twice at its two C-terminal palmitoyl-accepting cysteine residues, by the palmitoyl-transferring enzyme Akr1. Once palmitoylated, Yck2 traffics through the well characterized secretory pathway to the plasma membrane where it participates in many cellular functions, including bud morphogenesis, cytokinesis, nutrient sensing, and receptor internalization. While the hydrophilic Yck2 is presumably synthesized on cytosolic ribosomes, it gains access to the membrane system by interaction with the six transmembrane-spanning Golgi-localized Akr1. Since palmitoylation occurs at membranes and the palmitoyl-transferases are localized to membranes, one key question our lab has been asking is, "How does Yck2 locate Akr1?" This is a general problem for exclusively palmitoylated hydrophilic proteins because while other lipid modifications occur either co-translationally or in the cytoplasm and provide an immediate introduction to membranes, Yck2 must somehow traffic from its place of synthesis to Akr1.

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