{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86804"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86804","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Regulation of Molecular Motors by Glycogen Synthase Kinase 3β (GSK3β) and Presenilin (PS) During Axonal Transport","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Banerjee, Rupkatha"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gunawardena, Shermali","Biological Sciences"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-25T23:22:56Z","date_published":"2025-02-25T23:22:56Z","updated_at":"2026-07-27T19:05:37Z","subjects":["biology","neurosciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86804","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gunawardena, Shermali","Biological Sciences"]},{"key":"dc:creator","label":"Author","values":["Banerjee, Rupkatha"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-25T23:22:56Z","2020","2020-07-09 04:42:13"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["biology","neurosciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86804"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Within axons, molecular motors transport essential components required for neuronal function, maintenance, and viability. Defects in axonal transport have been implicated in many neurodegenerative diseases including Alzheimer's disease (AD). Although multiple levels of regulation must exist for proper transport of cargoes along axons, little is known about these mechanisms. Previous work in our lab showed that Presenilin (PS), a gene implicated in AD, and Glycogen synthase kinase 3β (GSK3β), regulates axonal transport, however, the mechanism by which these proteins function was unknown. In my work, we tested the overall hypothesis that PS and GSK3β regulate motor function during axonal transport. In chapter 2, we hypothesized that PS regulates GSK3β-mediated functions on motor proteins in vivo. We found that functional PS with an intact loop region is essential for the rescue of GSK3β-mediated transport defects, while disruption of PS loop or expression of a non-functional PS variant failed to rescue axonal blockages in vivo. We proposed a scaffolding mechanism for PS in which the loop region sequesters GSK3β away from motors for the proper regulation of motor function. Further, since active-GSK3β associated with and phosphorylated KHC (kinesin heavy chain) in vitro, in chapter 3, we hypothesized that GSK3β phosphorylation site on KHC is essential for kinesin-1 function in vivo. We identified a functional GSK3β phosphorylation site, S314, in the Drosophila KHC motor domain. Our in vitro results led us to propose that GSK3β phosphorylation at S314 acts as a stop for kinesin-1, while the loss of phosphorylation at this site causes uncoordinated motility, perhaps by decreasing kinesin's ATPase activity. Further, endogenous loss of GSK3β-phosphorylation at S314 decreased kinesin-1 attachment to MTs and membranes, mitochondrial motility in vivo, and/or kinesin motor ATPase activity. Together, our observations suggest a model in which GSK3β regulates kinesin-1 motor activity in vivo via differential phosphorylation. These findings have important implications for our understanding of the complex regulatory mechanisms that exist for controlling motor protein activity during axonal transport in vivo.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulation of Molecular Motors by Glycogen Synthase Kinase 3β (GSK3β) and Presenilin (PS) During Axonal Transport"]}]}],"canonical_facts":{"dc:contributor":["Gunawardena, Shermali","Biological Sciences"],"dc:creator":["Banerjee, Rupkatha"],"dc:date":["2025-02-25T23:22:56Z","2020","2020-07-09 04:42:13"],"dc:description":["Ph.D.","Within axons, molecular motors transport essential components required for neuronal function, maintenance, and viability. Defects in axonal transport have been implicated in many neurodegenerative diseases including Alzheimer's disease (AD). Although multiple levels of regulation must exist for proper transport of cargoes along axons, little is known about these mechanisms. Previous work in our lab showed that Presenilin (PS), a gene implicated in AD, and Glycogen synthase kinase 3β (GSK3β), regulates axonal transport, however, the mechanism by which these proteins function was unknown. In my work, we tested the overall hypothesis that PS and GSK3β regulate motor function during axonal transport. In chapter 2, we hypothesized that PS regulates GSK3β-mediated functions on motor proteins in vivo. We found that functional PS with an intact loop region is essential for the rescue of GSK3β-mediated transport defects, while disruption of PS loop or expression of a non-functional PS variant failed to rescue axonal blockages in vivo. We proposed a scaffolding mechanism for PS in which the loop region sequesters GSK3β away from motors for the proper regulation of motor function. Further, since active-GSK3β associated with and phosphorylated KHC (kinesin heavy chain) in vitro, in chapter 3, we hypothesized that GSK3β phosphorylation site on KHC is essential for kinesin-1 function in vivo. We identified a functional GSK3β phosphorylation site, S314, in the Drosophila KHC motor domain. Our in vitro results led us to propose that GSK3β phosphorylation at S314 acts as a stop for kinesin-1, while the loss of phosphorylation at this site causes uncoordinated motility, perhaps by decreasing kinesin's ATPase activity. Further, endogenous loss of GSK3β-phosphorylation at S314 decreased kinesin-1 attachment to MTs and membranes, mitochondrial motility in vivo, and/or kinesin motor ATPase activity. Together, our observations suggest a model in which GSK3β regulates kinesin-1 motor activity in vivo via differential phosphorylation. These findings have important implications for our understanding of the complex regulatory mechanisms that exist for controlling motor protein activity during axonal transport in vivo.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86804"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["biology","neurosciences"],"dc:title":["Regulation of Molecular Motors by Glycogen Synthase Kinase 3β (GSK3β) and Presenilin (PS) During Axonal Transport"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:37Z"}