Interaction of the Goldfish Kainate Receptor with G Proteins in a Novel Model System

Cornell Univ - State: Awds Made Prior May 2010, Ithaca NY

Investigators

Abstract

Information in the brain is transmitted from one nerve cell to another by the release of a messenger, called a neurotransmitter, from the presynaptic cell which diffuses across the small space and interacts with a receptor imbedded in the membrane of the postsynaptic cell. The amino acid glutamate is the most prevalent excitatory neurotransmitter in the brain. Glutamate binds to a receptor protein, which responds by opening a channel between the outside and inside of a cell allowing positively charged ions to flow across the cell membrane. Dr. Oswald is characterizing the structure, dynamics, and regulation of glutamate receptors using NMR spectroscopy, which provides details on the level of individual atoms. The first half of the project will focus on the glutamate-binding site, using a soluble form of the portion of the protein that interacts with glutamate. Specific dynamic processes will be studied, which are hypothesized to control the kinetics aspects of channel opening and closing. This is of particular interest because different kinetic processes for different glutamate receptors control many aspects of neuronal function, in particular learning and memory. The approach used in these studies is unique in that kinetics can be related directly to individual atoms. The second half will focus on the interaction of intracellular portions of one glutamate receptor, the NMDA receptor, with intracellular control factors. The structure of the NMDA receptor bound to a control factor will be determined which in turn has relevance to understanding the complex events associated with processes underlying learning and memory. Undergraduate students, underrepresented minorities, and a collaborator from an undergraduate institution will be involved in all aspects of this project. The molecular characterization of glutamate receptors will have broad importance to society. This includes such diverse areas as learning and memory and the development of biologically-based sensor technology.