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Regulation of glutamate receptors by striatal‐enriched tyrosine phosphatase 61 (STEP 61 )
Author(s) -
Won Sehoon,
Roche Katherine W.
Publication year - 2020
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp278703
Subject(s) - synaptic plasticity , ampa receptor , microbiology and biotechnology , protein tyrosine phosphatase , biology , silent synapse , phosphorylation , glutamate receptor , tyrosine phosphorylation , fyn , neurotransmission , long term depression , nmda receptor , neuroscience , biochemistry , receptor , proto oncogene tyrosine protein kinase src
Phosphorylation regulates glutamate receptor trafficking. The cytosolic C‐terminal domains of both NMDA receptors (NMDARs) and AMPA receptors (AMPARs) have distinct motifs, which are substrates for serine/threonine and tyrosine phosphorylation. Decades of research have shown how phosphorylation of glutamate receptors mediates protein binding and receptor trafficking, ultimately controlling synaptic transmission and plasticity. STEP is a protein tyrosine phosphatase (also known as PTPN5), with several isoforms resulting from alternative splicing. Targets of STEP include a variety of important synaptic substrates, among which are the tyrosine kinase Fyn and glutamate receptors. In particular, STEP 61 , the longest isoform, dephosphorylates the NMDAR subunit GluN2B and strongly regulates the expression of NMDARs at synapses. This interplay between STEP, Fyn and GluN2B‐containing NMDARs has been characterized by multiple groups. More recently, STEP 61 was shown to bind to AMPARs in a subunit‐specific manner and differentially regulate synaptic NMDARs and AMPARs. Because of its many effects on synaptic proteins, STEP has been implicated in regulating excitatory synapses during plasticity and playing a role in synaptic dysfunction in a variety of neurological disorders. In this review, we will highlight the ways in which STEP 61 differentially regulates NMDARs and AMPARs, as well as its role in plasticity and disease.