Dissertation/Thesis Abstract

The ESCRT machinery, required for endosomal trafficking, is a pH-signaling platform
by Boysen, Jacob, Ph.D., Columbia University, 2008, 195; 3348428
Abstract (Summary)

The evolution of complex signaling pathways, connecting external conditions to internal processes, has propelled life across the planet. Signaling follows a simple cellular outline: plasma membrane-embedded sensory receptors sense external conditions, initiate internal events leading to a response, and subsequent endocytic trafficking events degrade the receptor.

Here, I explore the interface between an endocytic process, the MVB pathway, and the pH-sensing Rim101 pathway. In response to alkaline pH, the Rim101 pathway coordinates proteolytic activation of transcription factor Rim101. Surprisingly I find that Rim101 proteolysis occurs on endosomal membranes and requires pH-regulated interaction between Bro1 Domain scaffold protein Rim20 and ESCRT-III subunit Snf7. In isolation, the Bro1 Domain interacts with Snf7 under all pH conditions; however, only under alkaline pH does there exist ESCRT-endosome platforms competent for assembling a stable Rim20-based complex capable of Rim101 proteolysis. I identify discrete and general inputs defining ESCRT-Bro1 Domain endosome populations, and subsequently build a simple and systematic protein-protein interaction assay based on endosome localization patterns.

Indexing (document details)
Advisor: Mitchell, Aaron P.
Commitee:
School: Columbia University
School Location: United States -- New York
Source: DAI-B 70/02, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Molecular biology, Cellular biology, Microbiology
Keywords: Bro1 Domain, ESCRT, Endosomal trafficking, Fungal virulence, Rim101, Trafficking, pH sensing
Publication Number: 3348428
ISBN: 9781109041231
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