Degree
Master of Science
Program
Anatomy and Cell Biology
Supervisor
Penuela, Silvia
Abstract
Pannexin 1 (PANX1) is a glycoprotein capable of forming large-pore single-membrane channels permeable to signaling molecules such as ATP. In this study, we interrogated different domains by introducing naturally occurring variants reported in melanoma and assessed their impact on the channel function of PANX1 at the cell surface. From this, we discovered a novel tyrosine phosphorylation site at Tyr150, that when disrupted via a missense mutation resulted in hypo-glycosylation and a greater capacity to traffic to the cell-surface and enhanced dye uptake. We have also uncovered a highly conserved ancestral allele, Gln5His, that has a greater allele frequency than the derived allele Gln5 in global and cancer cohorts but was not associated with cancer aggressiveness. Furthermore, Gln5His also did not impact glycosylation, cell-surface localization and channel-function in cancer cells. Our findings demonstrate the utility of studying naturally occurring variants in understanding diverse mechanisms that regulate PANX1 channel function.
Recommended Citation
Nouri Nejad, Daniel, "Biochemical and Functional Analyses of PANX1 Variants" (2019). Electronic Thesis and Dissertation Repository. 6230.
https://ir.lib.uwo.ca/etd/6230
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.