{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/28949"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/28949","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Biochemical and Functional Analyses of PANX1 Variants","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Nouri Nejad, Daniel"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Anatomy and Cell Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Penuela, Silvia"],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019","date_published":"2019","updated_at":"2026-07-27T21:56:05Z","subjects":["Pannexin 1 (PANX1)","pannexin","tyrosine-phosphorylation","glycosylation","trafficking","polymorphism"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/28949","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Penuela, Silvia"]},{"key":"dc:creator","label":"Author","values":["Nouri Nejad, Daniel"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T16:16:55Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T16:16:55Z"]},{"key":"dc:date.issued","label":"Date","values":["2019"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Anatomy and Cell Biology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Pannexin 1 (PANX1)","pannexin","tyrosine-phosphorylation","glycosylation","trafficking","polymorphism"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/28949"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:title","label":"Title","values":["Biochemical and Functional Analyses of PANX1 Variants"]}]}],"canonical_facts":{"dc:contributor.advisor":["Penuela, Silvia"],"dc:creator":["Nouri Nejad, Daniel"],"dc:date.accessioned":["2025-07-10T16:16:55Z"],"dc:date.available":["2025-07-10T16:16:55Z"],"dc:date.issued":["2019"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.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. 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