Regulation of GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors

Hdl Handle:
http://hdl.handle.net/10675.2/611691
Title:
Regulation of GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors
Authors:
Chung, Connie
Abstract:
NMDA receptors (NMDARs) play a major role in the pathological events following excitotoxicity. Post-ischemic activation of NMDARs has been linked to opposing signaling that mediates pro-survival or pro-death activity. This dichotomy is largely due to distinct GluN2 subunit compositions governing important receptor functions including channel properties, receptor trafficking, and synaptic localization. Compared to GluN2A- and GluN2B-containing NMDARs, the trafficking of GluN2C in non-cerebellar granule neurons is less well understood. Moreover, the role of GluN2C following cerebral ischemia remains unknown. Here, we report 14-3-3 isoform-specific binding and regulation of GluN2C. Our findings highlight the isoform-specific structural and functional differences within the 14-3-3 family of proteins which determine GluN2C binding and its essential role in targeting the receptor to the cell surface to facilitate glutamatergic neurotransmission. Next, we sought to investigate the role of GluN2C following cerebral ischemia. We show that GluN2C expression promotes neuronal survival as a homeostatic mechanism by which intracellular Ca2+ levels are maintained by upregulation of GluN2C. Through such a mechanism, not only the intracellular Ca2+ level but also NMDAR signaling can be maintained at equilibrium.
Affiliation:
Department of Neuroscience and Regenerative Medicine
Issue Date:
3-Jun-2016
URI:
http://hdl.handle.net/10675.2/611691
Type:
Dissertation
Language:
en
Description:
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Appears in Collections:
Department of Neuroscience & Regenerative Medicine Theses and Dissertations; Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorChung, Connieen
dc.date.accessioned2016-06-03T15:09:26Zen
dc.date.availableEmbargoed until 8/2/2018en
dc.date.issued2016-06-03en
dc.identifier.urihttp://hdl.handle.net/10675.2/611691en
dc.descriptionThe file you are attempting to access is currently restricted to Augusta University. Please log in with your NetID if off campus. Record is embargoed until 5/2/2018en
dc.description.abstractNMDA receptors (NMDARs) play a major role in the pathological events following excitotoxicity. Post-ischemic activation of NMDARs has been linked to opposing signaling that mediates pro-survival or pro-death activity. This dichotomy is largely due to distinct GluN2 subunit compositions governing important receptor functions including channel properties, receptor trafficking, and synaptic localization. Compared to GluN2A- and GluN2B-containing NMDARs, the trafficking of GluN2C in non-cerebellar granule neurons is less well understood. Moreover, the role of GluN2C following cerebral ischemia remains unknown. Here, we report 14-3-3 isoform-specific binding and regulation of GluN2C. Our findings highlight the isoform-specific structural and functional differences within the 14-3-3 family of proteins which determine GluN2C binding and its essential role in targeting the receptor to the cell surface to facilitate glutamatergic neurotransmission. Next, we sought to investigate the role of GluN2C following cerebral ischemia. We show that GluN2C expression promotes neuronal survival as a homeostatic mechanism by which intracellular Ca2+ levels are maintained by upregulation of GluN2C. Through such a mechanism, not only the intracellular Ca2+ level but also NMDAR signaling can be maintained at equilibrium.en
dc.language.isoenen
dc.subjectGluN2cen
dc.subjectNMDA Receptoren
dc.subjectIschemiaen
dc.subjectTraffickingen
dc.titleRegulation of GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptorsen
dc.typeDissertationen
dc.contributor.departmentDepartment of Neuroscience and Regenerative Medicineen
dc.contributor.committeememberErgul. Adviye Brann, Darrell W Kim, Jimok Xu, Juianhuaen
dc.description.advisorChen, Bo-Shiunen
dc.description.degreeDoctor of Philosophy with a Major in Molecular Medicineen
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