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.
|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|
|Xiao, Mei-Fang; Xu, Desheng; Craig, Michael T et al. (2017) NPTX2 and cognitive dysfunction in Alzheimer's Disease. Elife 6:|
|Agarwal, Amit; Wu, Pei-Hsun; Hughes, Ethan G et al. (2017) Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. Neuron 93:587-605.e7|
|Akassoglou, Katerina; Merlini, Mario; Rafalski, Victoria A et al. (2017) In Vivo Imaging of CNS Injury and Disease. J Neurosci 37:10808-10816|
|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|
|Perea, Gertrudis; Gómez, Ricardo; Mederos, Sara et al. (2016) Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks. Elife 5:|
|Ma, Zhiguo; Stork, Tobias; Bergles, Dwight E et al. (2016) Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour. Nature 539:428-432|
|Kim, Yu Shin; Anderson, Michael; Park, Kyoungsook et al. (2016) Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain. Neuron 91:1085-1096|
|Zhang-Hooks, YingXin; Agarwal, Amit; Mishina, Masayoshi et al. (2016) NMDA Receptors Enhance Spontaneous Activity and Promote Neuronal Survival in the Developing Cochlea. Neuron 89:337-50|
Showing the most recent 10 out of 23 publications