Investigations of The Structure-Function Relationship In Kainate Receptors Using FöRster Resonance Energy Transfer

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2019

Authors dc:creator

• Litwin, Douglas
• <p>0000-0002-6072-5498</p>

Contributors dc:contributor

• Vasanthi Jayaraman
• Darren F. Boehning
• Shane R. Cunha

• Ionotropic glutamate receptor
• Kainate receptor
• Single molecule FRET
• Biochemistry
• Biophysics
• Medicine and Health Sciences
• Molecular Biology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/966

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2013