Defense Date

2022

Document Type

Thesis

Degree Name

Master of Science

Department

Biology

First Advisor

Derek Prosser

Second Advisor

Alaattin Kaya

Third Advisor

Sarah Rothschild

Fourth Advisor

Jason Newton

Abstract

Abstract

Endocytosis is a fundamental cellular process that mediates internalization of membranes, proteins, and nutrients in all eukaryotes. In the past 40 years, the molecular machinery that regulates endocytosis has been studied extensively in yeast and mammalian cells to better understand the process. In this time, we have learned that a predominant pathway known as clathrin-mediated endocytosis (CME) utilizes the coat protein clathrin to stabilize vesicle formation. However, a variety of clathrin-independent endocytic (CIE) pathways exist that remain poorly understood. The first CIE pathway in budding yeast, an important model organism used for genetic studies of cellular function, was recently identified and was shown to require the cell wall stress sensor Mid2, the guanine nucleotide exchange factor Rom1, and its actin-modulating substrate, the small GTPase Rho1. Initial studies revealed that CIE in yeast appears to be more active when cells are grown at high osmolarity, suggesting that signal transduction pathways involved in osmoregulation may contribute to endocytosis. This study assesses endocytic roles for components of the high-osmolarity glycerol (HOG) pathway, which is a well-studied physiological regulator of osmolarity in yeast. By manipulating HOG1 and its upstream regulators, I show that a stress-responsive mitogen-activated protein kinase (MAPK) cascade is necessary for activation of, and functions in concert with, the Rho1-dependent CIE pathway. Thus, this work establishes novel relationships between signal transduction and membrane trafficking pathways that may apply broadly in eukaryotes, and provides insight into physiological factors that regulate clathrin-independent endocytosis.

Rights

© Ahmed Z. Al Ani

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-11-2022

Available for download on Tuesday, August 10, 2027

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