Cell Reports (Nov 2020)
AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF
- 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
Affiliations
- George K.E. Umanah
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
- Mehdi Ghasemi
- Department of Neurology, University of Massachusetts School of Medicine, Worcester, MA 01655, USA
- Xiling Yin
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Melissa Chang
- University of California, Irvine, School of Medicine, Irvine, CA 92697-3950, USA
- Jin Wan Kim
- University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Jianmin Zhang
- Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Beijing 100005, China
- Erica Ma
- Johns Hopkins University Krieger School of Arts and Sciences, Baltimore, MD 21205, USA
- Leslie A. Scarffe
- Division of Neurology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada
- Yun-Il Lee
- Division of Biotechnology, Well Aging Research Center, DGIST, Daegu, Republic of Korea
- Rong Chen
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Kavya Tangella
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Amy McNamara
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Leire Abalde-Atristain
- Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
- Mohamad A. Dar
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Samuel Bennett
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Marisol Cortes
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Shaida A. Andrabi
- Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Paschalis-Thomas Doulias
- Department of Pediatrics, Children’s Hospital of Philadelphia Research Institute, The University of Pennsylvania, Philadelphia, PA 19104, USA
- Harry Ischiropoulos
- Department of Pediatrics, Children’s Hospital of Philadelphia Research Institute, The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmacology, The University of Pennsylvania, Philadelphia, PA 19104, USA
- Ted M. Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, University of Massachusetts School of Medicine, Worcester, MA 01655, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
- Valina L. Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, University of Massachusetts School of Medicine, Worcester, MA 01655, USA; Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
- Journal volume & issue
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Vol. 33,
no. 5
p. 108329
Abstract
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.
