Schnetkamp, PaulJalloul, Ali2016-05-032016-05-0320162016Jalloul, A. (2016). Characterization of Different Isoforms of the K+-dependent Na+- Ca2+ Exchangers: A Look into Ca2+ Coordination and Functional Consequences of Mutations Associated with Different Genetic Diseases (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25272http://hdl.handle.net/11023/2940K+-dependent Na+-Ca2+ exchangers (NCKXs) belong to the Solute Carrier 24 gene family of membrane transporters. Five different exchangers have been identified in humans and contribute to many biological processes including vision, enamel maturation, Melanocortin-4-receptor-dependent satiety, olfaction and skin pigmentation. Here, I examined the differences in cation coordination of NCKX1-4 and tested the effect of single residue substitutions in the α-repeats on Ca2+ affinity in NCKX2. In addition, I investigated the functional consequences of mutations in different NCKX genes associated with genetic diseases. I measured NCKX-mediated Ca2+ transport activity of WT and mutant NCKX proteins while manipulating external or internal ion concentrations. I concluded that the differences observed among these exchangers do not explain the variation in their tissue distribution. Also, 13 single residue substitutions significantly lowered Ca2+ affinity in NCKX2. Moreover, the functional data presented about the mutations associated with genetic diseases support that the genetic analysis describing these mutations.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.GeneticsBiology--MolecularNeuroscienceDentistryBiochemistrySodium Calcium ExchangerNCKX proteinsFluorescent AssaysIon affinitymutagenesis Analysisgenetic diseasesmaster thesis10.11575/PRISM/25272