Phosphorylation of the AMPA receptor subunit GluA1 regulates clathrin-mediated receptor internalization.

Autor:	Sathler MF; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, 540 First Avenue, New York, NY 10016, USA.; Department of Biomedical Sciences, 1617 Campus Delivery, Colorado State University, Fort Collins, CO 80525, USA.; Neuroscience Program, Department of Physiology and Pharmacology, Rua São João Batista, 187, Sala 428, Fluminense Federal University, Niterói, RJ 24020-005, Brazil., Khatri L; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, 540 First Avenue, New York, NY 10016, USA., Roberts JP; Molecular, Cellular and Integrative Neurosciences Program, Colorado State University, Fort Collins, CO 80523, USA., Schmidt IG; Molecular, Cellular and Integrative Neurosciences Program, Colorado State University, Fort Collins, CO 80523, USA., Zaytseva A; Molecular, Cellular and Integrative Neurosciences Program, Colorado State University, Fort Collins, CO 80523, USA., Kubrusly RCC; Neuroscience Program, Department of Physiology and Pharmacology, Rua São João Batista, 187, Sala 428, Fluminense Federal University, Niterói, RJ 24020-005, Brazil., Ziff EB; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, 540 First Avenue, New York, NY 10016, USA., Kim S; Department of Biomedical Sciences, 1617 Campus Delivery, Colorado State University, Fort Collins, CO 80525, USA.; Molecular, Cellular and Integrative Neurosciences Program, Colorado State University, Fort Collins, CO 80523, USA.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2021 Sep 01; Vol. 134 (17). Date of Electronic Publication: 2021 Sep 07.
DOI:	10.1242/jcs.257972
Abstrakt:	Synaptic strength is altered during synaptic plasticity by controlling the number of AMPA receptors (AMPARs) at excitatory synapses. During long-term potentiation and synaptic upscaling, AMPARs are accumulated at synapses to increase synaptic strength. Neuronal activity leads to phosphorylation of AMPAR subunit GluA1 (also known as GRIA1) and subsequent elevation of GluA1 surface expression, either by an increase in receptor forward trafficking to the synaptic membrane or a decrease in receptor internalization. However, the molecular pathways underlying GluA1 phosphorylation-induced elevation of surface AMPAR expression are not completely understood. Here, we employ fluorescence recovery after photobleaching (FRAP) to reveal that phosphorylation of GluA1 serine 845 (S845) predominantly plays a role in receptor internalization, rather than forward trafficking, during synaptic plasticity. Notably, internalization of AMPARs depends upon the clathrin adaptor AP2, which recruits cargo proteins into endocytic clathrin-coated pits. In fact, we further reveal that an increase in GluA1 S845 phosphorylation upon two distinct forms of synaptic plasticity diminishes the binding of the AP2 adaptor, reducing internalization and resulting in elevation of GluA1 surface expression. We thus demonstrate a mechanism of GluA1 phosphorylation-regulated clathrin-mediated internalization of AMPARs. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2021. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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