Department of Neurology
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Enzymes and Coenzymes | Neuroscience and Neurobiology
The regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-d-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase and N-ethylmaleimide-sensitive factor (NSF). S-nitrosylation of Thorase stabilizes Thorase-AMPAR complexes and enhances the internalization of AMPAR and interaction with protein-interacting C kinase 1 (PICK1). S-nitrosylated NSF is dependent on the S-nitrosylation of Thorase via trans-nitrosylation, which modulates the surface insertion of AMPARs. In the presence of the S-nitrosylation-deficient C137L Thorase mutant, AMPAR trafficking, long-term potentiation, and long-term depression are impaired. Overall, our data suggest that both S-nitrosylation and interactions of Thorase and NSF/PICK1 are required to modulate AMPAR-mediated synaptic plasticity. This study provides critical information that elucidates the mechanism underlying Thorase and NSF-mediated trafficking of AMPAR complexes.
AMPAR, ATAD1, GluA2, N-ethylmaleimide-sensitive factor, N-methyl-d-aspartate receptor, NMDAR, NSF, PICK1, S-nitrosylation, endocytosis, exocytosis, protein-interacting C kinase 1, thorase, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
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Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Umanah GKE, Ghasemi M, Yin X, Chang M, Kim JW, Zhang J, Ma E, Scarffe LA, Lee YI, Chen R, Tangella K, McNamara A, Abalde-Atristain L, Dar MA, Bennett S, Cortes M, Andrabi SA, Doulias PT, Ischiropoulos H, Dawson TM, Dawson VL. AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF. Cell Rep. 2020 Nov 3;33(5):108329. doi: 10.1016/j.celrep.2020.108329. PMID: 33147468; PMCID: PMC7737632. Link to article on publisher's site
Umanah GK, Ghasemi M, Dawson VL. (2020). AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF. Open Access Publications by UMass Chan Authors. https://doi.org/10.1016/j.celrep.2020.108329. Retrieved from https://escholarship.umassmed.edu/oapubs/4453
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