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dc.contributor.advisorHamilton, Kirk
dc.contributor.authorLee, Shih-Liang
dc.date.available2015-02-11T02:08:32Z
dc.date.copyright2015
dc.identifier.citationLee, S.-L. (2015). The degradation of KCa3.1 in FRT polarised epithelium (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/5457en
dc.identifier.urihttp://hdl.handle.net/10523/5457
dc.description.abstractThe intermediate conductance calcium activated potassium channel (KCa3.1) has a prominent role in numerous physiological functions, and has recently emerged as the main therapeutic target for many disorders and diseases ranging from lymphoma to Alzheimer’s disease. Much is known about the physiology and pharmacology of this channel, but how the numbers of the channel are regulated at the cell surface remains elusive today. Previous studies aimed to unravel the degradation pathway of KCa3.1 are predominantly based on non-polarised models, as KCa3.1 is widely expressed in polarised epithelial tissues, it is likely that the degradation pathway can present different patterns. In this study, I investigated the key molecular components that regulate the degradation of KCa3.1 using polarised epithelium generated by Fisher rat thyroid (FRT) cells stably expressing KCa3.1. Using immunoblot and Ussing chamber techniques, I demonstrated that KCa3.1 is degraded via an ubiquitin dependent pathway. Inhibition of E1 ubiquitin activating enzyme via UBEI-41 crippled the ability for the cells to internalise the channel, shown by the increase of surface channel expression and DC-EBIO sensitive K+ current. Furthermore, the involvement of deubiquitinases and degradation by the lysosome were also confirmed by treating the cells with PR-619 and leupeptin/pepstatin, respectively; which significantly decreased the rate of membrane KCa3.1 degradation. These findings are the first to demonstrate the involvement of ubiquitin in the degradation of KCa3.1 within a polarised epithelium.
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectPhysiology
dc.subjectKCa3.1
dc.subjectPotassium
dc.subjectUbiquitin
dc.subjectESCRT
dc.titleThe degradation of KCa3.1 in FRT polarised epithelium
dc.typeThesis
dc.date.updated2015-02-11T02:01:03Z
dc.language.rfc3066en
thesis.degree.disciplinePhysiology
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.interloanyes
otago.openaccessAbstract Only
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