Glutamate-AMPA receptors are the key mediators of excitatory transmission of which GluA1 is a major subtype. GluA1's conductance is critically determined by phosphorylation at serine-831. We recently discovered that nitric oxide (NO) nitrosylates GluA1 at a specific cysteine, C875. and that this nitrosylation determines S831 phosphorylation. We plan to elucidate mechanisms underlying this important mode of regulation. We will also explore the impact of hydrogen sulfide (H2S) modifying, via sulfhydration, C875 in presumed reciprocity with nitrosylation. We earlier showed that nitrosylation of stargazin, a major auxiliary protein of AMPA receptors, determines GluA1 conductance. We will explore regulation of this process and how it interfaces with gasotransmitter influences exerted directly upon GluA1.
Learning, memory and other major brain functions are determined by neurotransmission involving the amino acid glutamate acting upon AMPA receptors. Our research shows how gasotransmitters. molecules such as nitric oxide and hydrogen sulfide, regulate these processes. This work clarifies fundamental aspects of brain function and affords an avenue to developing therapeutic agents for brain disease.
| Piard, Juliette; Hu, Jia-Hua; Campeau, Philippe M et al. (2018) FRMPD4 mutations cause X-linked intellectual disability and disrupt dendritic spine morphogenesis. Hum Mol Genet 27:589-600 |
| Diering, Graham H; Huganir, Richard L (2018) The AMPA Receptor Code of Synaptic Plasticity. Neuron 100:314-329 |
| Heo, Seok; Diering, Graham H; Na, Chan Hyun et al. (2018) Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover. Proc Natl Acad Sci U S A 115:E3827-E3836 |
| Xiao, Mei-Fang; Xu, Desheng; Craig, Michael T et al. (2017) NPTX2 and cognitive dysfunction in Alzheimer's Disease. Elife 6: |
| Ryu, Changhyeon; Jang, Dong Cheol; Jung, Dayoon et al. (2017) STIM1 Regulates Somatic Ca2+ Signals and Intrinsic Firing Properties of Cerebellar Purkinje Neurons. J Neurosci 37:8876-8894 |
| Akassoglou, Katerina; Merlini, Mario; Rafalski, Victoria A et al. (2017) In Vivo Imaging of CNS Injury and Disease. J Neurosci 37:10808-10816 |
| Li, Ang; Liang, Wenxuan; Guan, Honghua et al. (2017) Focus scanning with feedback-control for fiber-optic nonlinear endomicroscopy. Biomed Opt Express 8:2519-2527 |
| Wang, Qiang; Chiu, Shu-Ling; Koropouli, Eleftheria et al. (2017) Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons. Neuron 96:1084-1098.e7 |
| Roth, Richard H; Zhang, Yong; Huganir, Richard L (2017) Dynamic imaging of AMPA receptor trafficking in vitro and in vivo. Curr Opin Neurobiol 45:51-58 |
| Diering, Graham H; Nirujogi, Raja S; Roth, Richard H et al. (2017) Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science 355:511-515 |
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