Regulation of glutamate receptors by striatal‐enriched tyrosine phosphatase 61 (STEP61)
Open accessAbstract
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. image
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Genes related to structural adhesion and stability were enriched in the ventral horn of the spinal cord.
“In contrast, genes related to structural adhesion and stability were enriched in the ventral horn of the spinal cord, including (1) genes related to cell-cell adhesion such as Lrrtm3, Cntn5, Cdh18, and Sdk1; (2) genes related to perineuronal net components such as Bcan (Brevican) and Tnr (Tenascin R), and genes related to limiting the signal transduction pathways associated with LTP such as Ptpn5”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [33]
Within the ventral horn, structural stability-related genes included components of perineuronal nets such as Tnr (Tenascin-R), as well as adhesion molecules such as Sdk1 and intracellular signaling components such as Ptpn5 (STEP).
“Within the ventral horn, this included components of perineuronal nets (which are thought to restrict plasticity and had been previously detected in the ventral spinal cord110,111) such as Tnr (Tenascin-R), as well as adhesion molecules such as Sdk1 and intracellular signaling components such as Ptpn5 (STEP) which de-phosphorylates CAMK2α, NMDA receptors, and ERK kinases33.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [33]
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- Authors
- Won, S., & Roche, K. W.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Roche, Katherine W.
- ORCID
- Roche, Katherine W.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2020-04-29
- Volume
- 599
- Issue
- 2
- Pages
- 443-451
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC11526339
- OpenAlex
- W3011267488
- Cited by
- 34
- References
- 51
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- onlinelibrary.wiley.com/termsAndConditions#vor (vor)
- Locations
- The Journal of Physiology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- McGill University
- International Society for Neurochemistry
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders
- National Institute of Neurological Disorders and Stroke (ZIANS002994)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- protein tyrosine phosphatase, glutamate receptors, NMDA receptor, AMPA receptors, receptor trafficking, Fyn, synaptic plasticity, excitatory synapses, alternative splicing, neurological disorders
- MeSH terms
- Animals, Corpus Striatum, Synapses, Tyrosine, Receptors, N-Methyl-D-Aspartate, Protein Tyrosine Phosphatases, Rats, Sprague-Dawley, Receptors, AMPA, Rats
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