Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Electronic Theses and Dissertations bannerUCSF

Elucidating the role of ubiquitin in controlling the endocytic trafficking of opioid receptors

Abstract

This dissertation examines the role of ubiquitination in regulating the endocytic trafficking of opioid receptors, members of the large superfamily of seven-transmembrane receptors (7TMRs). The introduction provides a basic overview of 7TMR biology and diversity, examines the role of endocytic trafficking in modulating receptor-mediated signal strength and duration, presents current models for protein sorting in the endocytic pathway, and investigates various functions of ubiquitin in regulating trafficking decisions. The second and third chapters explore the role of ubiquitin in controlling the destruction of δ-opioid receptors after their sorting to lysosomes. In chapter four, a new function of ubiquitin is identified that allows μ-opioid receptors to control the dynamics of receptor-containing clathrin-coated pits and ultimately, their own endocytosis. The fifth chapter presents findings for an additional role of μ-opioid receptor ubiquitination later in the endocytic pathway, modulating receptor destruction after lysosomal sorting, that provides further support for models developed through study of the δ-opioid receptor. The included work used a combination of live-cell imaging, flow cytometric analysis, biochemistry, and genetic manipulations to address the role of ubiquitin in opioid receptor trafficking. Two additional studies that I contributed to during my graduate career, one published (Yudowski et al., 2009) and one under preparation, were excluded as they were beyond the main focus of this dissertation.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View