AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF

Autor: George K.E. Umanah, Mehdi Ghasemi, Xiling Yin, Melissa Chang, Jin Wan Kim, Jianmin Zhang, Erica Ma, Leslie A. Scarffe, Yun-Il Lee, Rong Chen, Kavya Tangella, Amy McNamara, Leire Abalde-Atristain, Mohamad A. Dar, Samuel Bennett, Marisol Cortes, Shaida A. Andrabi, Paschalis-Thomas Doulias, Harry Ischiropoulos, Ted M. Dawson, Valina L. Dawson
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Reports, Vol 33, Iss 5, Pp 108329- (2020)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2020.108329
Popis: Summary: The regulation of α-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.
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