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.
|Advisor:||Mitchell, Aaron P.|
|School Location:||United States -- New York|
|Source:||DAI-B 70/02, Dissertation Abstracts International|
|Subjects:||Molecular biology, Cellular biology, Microbiology|
|Keywords:||Bro1 Domain, ESCRT, Endosomal trafficking, Fungal virulence, Rim101, Trafficking, pH sensing|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be