{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80587"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80587","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Understanding the Scaffolding Mechanisms of Ion Channels by Magi Proteins","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Krishnan, Jahnavi; 0000-0002-4898-8244"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Bhattacharjee, Arindam","Pharmacology and Toxicology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-10-28T17:37:43Z","date_published":"2019-10-28T17:37:43Z","updated_at":"2026-07-27T19:05:23Z","subjects":["pharmacology","neurosciences","molecular biology"],"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/10477/80587","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bhattacharjee, Arindam","Pharmacology and Toxicology"]},{"key":"dc:creator","label":"Author","values":["Krishnan, Jahnavi; 0000-0002-4898-8244"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-10-28T17:37:43Z","2019","2019-08-05 12:30:44"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmacology","neurosciences","molecular biology"]}]},{"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/10477/80587"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Ion channels play important neuromodulatory functions in neurons of the PNS and CNS. In this study, we are focusing on two important ion channels of the nervous system. The first being Slick (KCNT2), a sodium-activated potassium channel notably expressed in the DRG is responsible for reducing pain and nociception due to its outward potassium current. The second being GluA1, a subunit of the AMPA receptor, widely expressed in the brain and is responsible for learning and memory formation. Through this study, we are exploring a sub-class of scaffolding proteins of the MAGUK family called Magi proteins and their interactions with these channels. We identified the site of binding in the Slick channel N-terminus, a PPxY motif which interacts with the WW domain in Magi-1 leading to an overall increase in total protein expression of the Slick channel in CHO cells by protecting it from Ubiquitination by ubiquitin ligases (ULs) in the cytosol. Similarly, we observed an increase in total protein expression of GluA1 in HEK-293 cells when co-transfected with Magi-2 (SSCAM), another member of the Magi family and Nedd4L, a ubiquitin ligase shown to internalize and degrade GluA1 by recognizing a Lysine (K) at the 863rd position in the C-terminus. Based on these studies, we identified a novel motif in the GluA1 C-terminus that is recognized by WW domains present in both Magi proteins and ULs. These studies help understand cytosolic protein-protein interactions between GluA1, Nedd4L and Magi-2 and hence developing these sites as potential drug targets for the treatment of a spectrum of learning disorders, Alzheimer’s disease, dementia and epilepsy among others."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Understanding the Scaffolding Mechanisms of Ion Channels by Magi Proteins"]}]}],"canonical_facts":{"dc:contributor":["Bhattacharjee, Arindam","Pharmacology and Toxicology"],"dc:creator":["Krishnan, Jahnavi; 0000-0002-4898-8244"],"dc:date":["2019-10-28T17:37:43Z","2019","2019-08-05 12:30:44"],"dc:description":["M.S.","Ion channels play important neuromodulatory functions in neurons of the PNS and CNS. In this study, we are focusing on two important ion channels of the nervous system. The first being Slick (KCNT2), a sodium-activated potassium channel notably expressed in the DRG is responsible for reducing pain and nociception due to its outward potassium current. The second being GluA1, a subunit of the AMPA receptor, widely expressed in the brain and is responsible for learning and memory formation. Through this study, we are exploring a sub-class of scaffolding proteins of the MAGUK family called Magi proteins and their interactions with these channels. We identified the site of binding in the Slick channel N-terminus, a PPxY motif which interacts with the WW domain in Magi-1 leading to an overall increase in total protein expression of the Slick channel in CHO cells by protecting it from Ubiquitination by ubiquitin ligases (ULs) in the cytosol. Similarly, we observed an increase in total protein expression of GluA1 in HEK-293 cells when co-transfected with Magi-2 (SSCAM), another member of the Magi family and Nedd4L, a ubiquitin ligase shown to internalize and degrade GluA1 by recognizing a Lysine (K) at the 863rd position in the C-terminus. Based on these studies, we identified a novel motif in the GluA1 C-terminus that is recognized by WW domains present in both Magi proteins and ULs. These studies help understand cytosolic protein-protein interactions between GluA1, Nedd4L and Magi-2 and hence developing these sites as potential drug targets for the treatment of a spectrum of learning disorders, Alzheimer’s disease, dementia and epilepsy among others."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80587"],"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":["pharmacology","neurosciences","molecular biology"],"dc:title":["Understanding the Scaffolding Mechanisms of Ion Channels by Magi Proteins"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:23Z"}