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Rescue of Kidney Anion Exchanger 1 Trafficking Mutants
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- Author / Creator
- Chu, Carmen Y.S.
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The kidney anion exchanger 1 (kAE1) is crucial in the regulation of physiological pH by facilitating Cl-/HCO3- exchange. Inability to do so results in distal renal tubular acidosis (dRTA), which is more often due to mutations leading to mis-localization of kAE1, rather than complete abolishment of its functional activity. The purpose of this thesis is to understand the trafficking, turnover, and rescue of wildtype (WT) and trafficking mutants of the kAE1. Chemical chaperones and low temperature treatments were studied for their ability to rescue trafficking of G701D, C479W and R589H kAE1 mutants. G701D kAE1 was rescued by dimethyl sulfoxide (DMSO) and is functional at the membrane. The turnover of all kAE1 mutants studied was dependent on the proteasomal pathway, while G701D and WT kAE1 are also degraded via the lysosomal pathway. These studies provide essential information for developing rescue methods at the molecular level, targeting the source of the disease rather than the symptoms.
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- Subjects / Keywords
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- Graduation date
- Fall 2012
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.