Biochemical and Functional Analyses of PANX1 Variants

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.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Anatomy and Cell Biology

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2019

Author dc:creator

• Nouri Nejad, Daniel

Advisor dc:contributor.advisor

• Penuela, Silvia

• Pannexin 1 (PANX1)
• pannexin
• tyrosine-phosphorylation
• glycosylation
• trafficking
• polymorphism

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/28949

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/28949