Michael L. Prodromou

2nd Year Medical Student

Department: School of Medicine

Graduate Program: TBD

Advisor: Rotating Advisor, Lonnie Wollmuth

Abstract (rotation):

Preceptor: Dr. Lonnie Wollmuth, Department of Neurobiology and Behavior

Title: Subunits-Specific Contribution of NMDA Receptor Subunits to Channel and Gating

NMDA receptors (NMDARs) mediate a slow component of the synaptic response at the majority of excitatory synapses in the brain, contributing to fundamental physiological processes such as learning and memory and, when dysfunctional, to pathophysiological conditions such as neurodegenerative diseases, stroke and mental illness. NMDARs are obligate heteromultimers typically composed of NR1 and NR2 subunits with the different subunits underlying the functional versatility of NMDARs. To study the contribution of the different subunits to NMDAR channel structure and gating, we compared the effects of cysteine-reactive reagents on cysteines substituted in and around the M3 segments of the NR1 and NR2C subunits. As in NR1, the M3 segment in NR2C appears to be the only transmembrane segment that contributes to the deep or voltage dependent portion of the extracellular vestibule. This contribution, however, is subunit-specific with the NR1 M3 segment covering a greater portion of the central pore surface than the NR2C M3 segment. The state dependence of reactivity suggested that the M3 segments in both NR1 and NR2C subunits make central albeit structurally distinct roles in gating.

Publications:
(MSTP-supported publications indicated with an *)

*Alexander I. Sobolevsky, Michael L. Prodromou, Maria V. Yelshansky, and Lonnie P. Wollmuth. Subunit-specific Contribution of NMDA Receptor Subunits to Channel Structure and Gating. (Submitted)