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Title: Analyzing the Binding Interactions of Major  Histocompatibility Complex Class I at Neuronal Synapses
Authors: Kim, Hyunjean Catherine
Advisors: Boulanger, Lisa
Department: Molecular Biology
Class Year: 2014
Abstract: Although MHC class I has been well classified in the immune system as a class of antigen presenters, recent investigations have revealed a non- immune functions for these proteins in the brain. Hippocampal neurons that are deficient in cell-surface MHC class I have increased NMDAR-mediated currents, demonstrating a regulatory role of MHC class I. To explore the molecular mechanism by which MHC class I regulates NMDARs, this thesis investigated the binding interactions of MHC class I molecules with candidate binding partners spinophilin and PSD-95. Specifically, the intracellular domains of MHC class I proteins were studied by cloning the cytoplasmic tails into vectors for use in co-immunoprecipitation, overlay assays, and pull-down assays. Recombinant cytoplasmic tails of non-classical MHC class I protein T22 did not pull down endogenous PSD-95, although they did bind the recombinant PDZ domains of PSD-95. Due to experimental errors, the co-immunoprecipitation of classical MHC class I K recombinant cytoplasmic tails with hippocampal lysates was not conclusive. The results of this thesis suggest that T22 does not bind PSD-95. The regulatory role of MHC class I on NMDARs could contribute to NMDAR dysfunction in brain disorders, such as schizophrenia.
Extent: 95 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Molecular Biology, 1954-2020

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