{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/37408"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/37408","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Novel Roles of PACS-1 Within the Nucleus and the Regulated Secretory Pathway","abstract":"PACS-1 functions are explored in three linked sections: the investigation of PACS-1 nuclear trafficking, the impact of PACS-1 on calcium homeostasis, and PACS-1 regulation of membrane protein trafficking within the regulated secretory pathway. First, our results establish PACS-1 motifs that regulate nuclear localization through the classical nuclear trafficking pathway. Moreover, we have identified a novel interaction between PACS-1 and the nucleocytoplasmic RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), unveiling a PACS-1 nuclear trafficking function. Second, we defined a role for PACS-1 orchestrating intracellular calcium levels within corticotropic cells. We establish PACS-1 interactions with transient receptor potential cation channel 3 subfamily C (TRPC3) and extended synaptotagmin 1 (ESyt-1), demonstrating that PACS-1 controls the trafficking of these proteins to the plasma membrane. Furthermore, we identify ESyt-1 as a negative regulator of adrenocorticotropic hormone (ACTH) secretion that requires PACS-1 to complete this regulation. Third, we elucidated adaptor protein complex 1 (AP-1) residues that interact with PACS-1. We further demonstrate that PACS-1 interacts with the ACTH processing enzyme peptidylglycine alpha-amidating monooxygenase (PAM) and is required for sorting PAM into the regulated secretory pathway in corticotropic cells. In conclusion, this research significantly advances our understanding of PACS-1's diverse functions within cells. By identifying trafficking functions for PACS-1 within nucleocytoplasmic shuttling, membrane trafficking of calcium ion channels, and retaining essential prohormone processing proteins within the regulated secretory pathway, this research truly underscores the multifunctional roles PACS-1 executes to maintain cellular homeostasis.","abstract_html":"PACS-1 functions are explored in three linked sections: the investigation of PACS-1 nuclear trafficking, the impact of PACS-1 on calcium homeostasis, and PACS-1 regulation of membrane protein trafficking within the regulated secretory pathway. First, our results establish PACS-1 motifs that regulate nuclear localization through the classical nuclear trafficking pathway. Moreover, we have identified a novel interaction between PACS-1 and the nucleocytoplasmic RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), unveiling a PACS-1 nuclear trafficking function. Second, we defined a role for PACS-1 orchestrating intracellular calcium levels within corticotropic cells. We establish PACS-1 interactions with transient receptor potential cation channel 3 subfamily C (TRPC3) and extended synaptotagmin 1 (ESyt-1), demonstrating that PACS-1 controls the trafficking of these proteins to the plasma membrane. Furthermore, we identify ESyt-1 as a negative regulator of adrenocorticotropic hormone (ACTH) secretion that requires PACS-1 to complete this regulation. Third, we elucidated adaptor protein complex 1 (AP-1) residues that interact with PACS-1. We further demonstrate that PACS-1 interacts with the ACTH processing enzyme peptidylglycine alpha-amidating monooxygenase (PAM) and is required for sorting PAM into the regulated secretory pathway in corticotropic cells. In conclusion, this research significantly advances our understanding of PACS-1's diverse functions within cells. By identifying trafficking functions for PACS-1 within nucleocytoplasmic shuttling, membrane trafficking of calcium ion channels, and retaining essential prohormone processing proteins within the regulated secretory pathway, this research truly underscores the multifunctional roles PACS-1 executes to maintain cellular homeostasis.","abstract_has_math":false,"creators":["Trothen, Steven"],"institution":"The University of Western Ontario","degree_name":"Ph D","degree_level":null,"degree_discipline":"Microbiology and Immunology","degree_department":null,"school":null,"contributors":[],"advisors":["Dikeakos, Jimmy D."],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-11-23","date_published":"2023-11-23","updated_at":"2026-07-27T21:56:18Z","subjects":["membrane trafficking","nuclear transport","phosphofurin acidic cluster sorting protein 1","protein-protein interactions","store-operated calcium entry","regulated secretion"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/37408","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Dikeakos, Jimmy D."]},{"key":"dc:creator","label":"Author","values":["Trothen, Steven"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T21:34:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T21:34:38Z"]},{"key":"dc:date.issued","label":"Date","values":["2023-11-23"]},{"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":["Microbiology and Immunology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph D"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["membrane trafficking","nuclear transport","phosphofurin acidic cluster sorting protein 1","protein-protein interactions","store-operated calcium entry","regulated secretion"]}]},{"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/20.500.14721/37408"]}]},{"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":["PACS-1 functions are explored in three linked sections: the investigation of PACS-1 nuclear trafficking, the impact of PACS-1 on calcium homeostasis, and PACS-1 regulation of membrane protein trafficking within the regulated secretory pathway. First, our results establish PACS-1 motifs that regulate nuclear localization through the classical nuclear trafficking pathway. Moreover, we have identified a novel interaction between PACS-1 and the nucleocytoplasmic RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), unveiling a PACS-1 nuclear trafficking function. Second, we defined a role for PACS-1 orchestrating intracellular calcium levels within corticotropic cells. We establish PACS-1 interactions with transient receptor potential cation channel 3 subfamily C (TRPC3) and extended synaptotagmin 1 (ESyt-1), demonstrating that PACS-1 controls the trafficking of these proteins to the plasma membrane. Furthermore, we identify ESyt-1 as a negative regulator of adrenocorticotropic hormone (ACTH) secretion that requires PACS-1 to complete this regulation. Third, we elucidated adaptor protein complex 1 (AP-1) residues that interact with PACS-1. We further demonstrate that PACS-1 interacts with the ACTH processing enzyme peptidylglycine alpha-amidating monooxygenase (PAM) and is required for sorting PAM into the regulated secretory pathway in corticotropic cells. In conclusion, this research significantly advances our understanding of PACS-1's diverse functions within cells. By identifying trafficking functions for PACS-1 within nucleocytoplasmic shuttling, membrane trafficking of calcium ion channels, and retaining essential prohormone processing proteins within the regulated secretory pathway, this research truly underscores the multifunctional roles PACS-1 executes to maintain cellular homeostasis."]},{"key":"dc:title","label":"Title","values":["Novel Roles of PACS-1 Within the Nucleus and the Regulated Secretory Pathway"]}]}],"canonical_facts":{"dc:contributor.advisor":["Dikeakos, Jimmy D."],"dc:creator":["Trothen, Steven"],"dc:date.accessioned":["2025-07-10T21:34:38Z"],"dc:date.available":["2025-07-10T21:34:38Z"],"dc:date.issued":["2023-11-23"],"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":["PACS-1 functions are explored in three linked sections: the investigation of PACS-1 nuclear trafficking, the impact of PACS-1 on calcium homeostasis, and PACS-1 regulation of membrane protein trafficking within the regulated secretory pathway. First, our results establish PACS-1 motifs that regulate nuclear localization through the classical nuclear trafficking pathway. Moreover, we have identified a novel interaction between PACS-1 and the nucleocytoplasmic RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), unveiling a PACS-1 nuclear trafficking function. Second, we defined a role for PACS-1 orchestrating intracellular calcium levels within corticotropic cells. We establish PACS-1 interactions with transient receptor potential cation channel 3 subfamily C (TRPC3) and extended synaptotagmin 1 (ESyt-1), demonstrating that PACS-1 controls the trafficking of these proteins to the plasma membrane. Furthermore, we identify ESyt-1 as a negative regulator of adrenocorticotropic hormone (ACTH) secretion that requires PACS-1 to complete this regulation. Third, we elucidated adaptor protein complex 1 (AP-1) residues that interact with PACS-1. We further demonstrate that PACS-1 interacts with the ACTH processing enzyme peptidylglycine alpha-amidating monooxygenase (PAM) and is required for sorting PAM into the regulated secretory pathway in corticotropic cells. In conclusion, this research significantly advances our understanding of PACS-1's diverse functions within cells. By identifying trafficking functions for PACS-1 within nucleocytoplasmic shuttling, membrane trafficking of calcium ion channels, and retaining essential prohormone processing proteins within the regulated secretory pathway, this research truly underscores the multifunctional roles PACS-1 executes to maintain cellular homeostasis."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/37408"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["membrane trafficking","nuclear transport","phosphofurin acidic cluster sorting protein 1","protein-protein interactions","store-operated calcium entry","regulated secretion"],"dc:title":["Novel Roles of PACS-1 Within the Nucleus and the Regulated Secretory Pathway"],"dc:type":["thesis"],"thesis:degree_discipline":["Microbiology and Immunology"],"thesis:degree_name":["Ph D"]},"updated_at":"2026-07-27T21:56:18Z"}