Author ORCID Identifier

0000-0002-6072-5498

Date of Graduation

8-2019

Document Type

Dissertation (PhD)

Program Affiliation

Biochemistry and Molecular Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Vasanthi Jayaraman

Committee Member

Darren F. Boehning

Committee Member

Shane R. Cunha

Committee Member

Jeffrey A. Frost

Committee Member

Irina I. Serysheva

Abstract

Kainate receptors belong to the family of ion channels known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory synaptic transmission, modulate the release of presynaptic glutamate, and facilitate dendrite formation. Kainate receptors are unique among the ionotropic glutamate receptors in being modulated by sodium ions. They have also been implicated in the development of higher learning and epilepsy. In recent years a wealth of structural data has become available for the AMPA and NMDA classes; however, the structural characterization of kainate receptors has been limited. The work in this dissertation utilizes luminescence resonance energy transfer (LRET) and single-molecule Förster Resonance Energy Transfer (smFRET) in order to address this gap in the knowledge. We have characterized the structural arrangement and dynamics of the homomeric (GluK2) receptors and identified structural changes involved in the functional modulation by ions and auxiliary proteins. Additionally, we have characterized the arrangement and dynamics of the heteromeric (GluK2/GluK5). These data will build a foundation for the full biophysical characterization of kainate receptors; and contribute to the development of subunit-specific modulatory compounds to be used for disease therapies, and for more detailed characterization of brain function at the molecular level.

Keywords

Ionotropic glutamate receptor, Kainate receptor, Single molecule FRET

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