The STEP 61 interactome reveals subunit-specific AMPA receptor binding and synaptic regulation

Autor:	Katherine W. Roche, Sehoon Won, Roger A. Nicoll, Salvatore Incontro, Yan Li
Rok vydání:	2019
Předmět:	Multidisciplinary nervous system Chemistry musculoskeletal neural and ocular physiology Protein subunit Phosphatase NMDA receptor Phosphorylation AMPA receptor Protein tyrosine phosphatase Receptor Interactome Cell biology
Zdroj:	Proceedings of the National Academy of Sciences. 116:8028-8037
ISSN:	1091-6490 0027-8424
Popis:	Significance Striatal-enriched protein tyrosine phosphatase (STEP) regulates the trafficking and function of a variety of synaptic proteins, including receptors and protein kinases. In addition, STEP’s expression and activity are altered in many neuropsychiatric disorders. Here, we isolate the STEP 61 interactome, which includes known interactors such as NMDA receptor (NMDAR) subunits, PSD-95, and Fyn kinase. In addition, we identified the AMPA receptor (AMPAR) GluA2 subunit as a binding protein. We show that STEP 61 binds to the C termini of GluA2 and GluA3, but not GluA1. Furthermore, we show that STEP 61 dephosphorylates GluA2, thereby regulating synaptic GluA2-containing AMPARs via endocytosis and lysosomal degradation. STEP 61 preferentially regulates synaptic AMPARs and extrasynaptic NMDARs, revealing a role for STEP 61 in defining activity-dependent glutamate receptor localization.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ef6b173187ebab15d6cd3cd9eefdd74a https://doi.org/10.1073/pnas.1900878116 Zobrazit plný text záznamu