Electronic Thesis and Dissertation Repository

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.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Wednesday, July 01, 2020

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