Kainate receptors (KARs) are expressed throughout the central and peripheral nervous systems. One of three subfamilies of ionotropic glutamate receptors, KARs are localized both pre- and post-synaptically and exert important modulatory control over neural circuits. This modulatory role in circuit function makes them a potential actor in wide variety of neurological disorders, and they play an established role in pathological but not acute pain. The basic constituents of KARs, the pore-forming subunits, were identified over 25 years ago; since then, a vast amount of research has described both the cellular regulation of KAR subunits and the functional contribution of these receptors to excitatory and inhibitory signaling. Differential combinations of auxiliary and pore-forming subunits, post-transcriptional and post-translational modifications, and dynamic protein–protein interactions comprise a complex collective of molecules that constitutes native receptors. In this dissertation, I present work that furthers our understanding of two of these molecular KAR components: the auxiliary protein Neto2, and the N-glycan moieties attached to receptor subunits. In Chapter 2, I confirm Neto2 as a true KAR auxiliary protein, showing that it is a developmentally regulated constituent of KARs in peripheral sensory neurons that modulates neurite outgrowth. In Chapter 3, I show that changing the molecular content of recombinant KAR N-glycosylation alters functional properties of these receptors. Although auxiliary subunits and oligosaccharide chains are molecularly distinct, both are expected to be critical components of native KARs. Understanding their contribution to receptor function is critical to improving our knowledge of KAR function within neural circuits, the role of these receptors in cognition and disease, and their potential as therapeutic targets.

Last modified

• 03/13/2018

Creator

• Claire Vernon

DOI

• https://doi.org/10.21985/N2FH60

Subject

• Driskill Graduate Training Program in Life Sciences

Keyword

• Neurosciences

Date created

• 2017-01-01

Resource type

• Dissertation

Rights statement

• In Copyright