PMID- 26391783 OWN - NLM STAT- MEDLINE DCOM- 20160706 LR - 20181113 IS - 1756-6606 (Electronic) IS - 1756-6606 (Linking) VI - 8 IP - 1 DP - 2015 Sep 22 TI - Regulation of STEP61 and tyrosine-phosphorylation of NMDA and AMPA receptors during homeostatic synaptic plasticity. PG - 55 LID - 10.1186/s13041-015-0148-4 [doi] LID - 55 AB - BACKGROUND: Sustained changes in network activity cause homeostatic synaptic plasticity in part by altering the postsynaptic accumulation of N-methyl-D-aspartate receptors (NMDAR) and alpha-amino-3-hydroxyle-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), which are primary mediators of excitatory synaptic transmission. A key trafficking modulator of NMDAR and AMPAR is STriatal-Enriched protein tyrosine Phosphatase (STEP61) that opposes synaptic strengthening through dephosphorylation of NMDAR subunit GluN2B and AMPAR subunit GluA2. However, the role of STEP61 in homeostatic synaptic plasticity is unknown. FINDINGS: We demonstrate here that prolonged activity blockade leads to synaptic scaling, and a concurrent decrease in STEP61 level and activity in rat dissociated hippocampal cultured neurons. Consistent with STEP61 reduction, prolonged activity blockade enhances the tyrosine phosphorylation of GluN2B and GluA2 whereas increasing STEP61 activity blocks this regulation and synaptic scaling. Conversely, prolonged activity enhancement increases STEP61 level and activity, and reduces the tyrosine phosphorylation and level of GluN2B as well as GluA2 expression in a STEP61-dependent manner. CONCLUSIONS: Given that STEP61-mediated dephosphorylation of GluN2B and GluA2 leads to their internalization, our results collectively suggest that activity-dependent regulation of STEP61 and its substrates GluN2B and GluA2 may contribute to homeostatic stabilization of excitatory synapses. FAU - Jang, Sung-Soo AU - Jang SS AD - Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. sjang16@illinois.edu. AD - Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. sjang16@illinois.edu. FAU - Royston, Sara E AU - Royston SE AD - Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. sroysto2@illinois.edu. AD - Medical Scholars Program, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. sroysto2@illinois.edu. FAU - Xu, Jian AU - Xu J AD - Child Study Center, New Haven, CT, 06510, USA. jx38@connect.yale.edu. FAU - Cavaretta, John P AU - Cavaretta JP AD - Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. jpcav@yahoo.com. FAU - Vest, Max O AU - Vest MO AD - Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. vest2@illinois.edu. FAU - Lee, Kwan Young AU - Lee KY AD - Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. red3327@gmail.com. FAU - Lee, Seungbae AU - Lee S AD - Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. xbee888@gmail.com. FAU - Jeong, Han Gil AU - Jeong HG AD - Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. hjeong10@illinois.edu. FAU - Lombroso, Paul J AU - Lombroso PJ AD - Child Study Center, New Haven, CT, 06510, USA. paul.lombroso@yale.edu. AD - Department of Neurobiology and Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA. paul.lombroso@yale.edu. FAU - Chung, Hee Jung AU - Chung HJ AD - Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. chunghj@life.illinois.edu. AD - Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. chunghj@life.illinois.edu. LA - eng GR - R01 MH052711/MH/NIMH NIH HHS/United States GR - R01 MH091037/MH/NIMH NIH HHS/United States GR - MH052711/MH/NIMH NIH HHS/United States GR - MH091037/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150922 PL - England TA - Mol Brain JT - Molecular brain JID - 101468876 RN - 0 (NR2B NMDA receptor) RN - 0 (Receptors, AMPA) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 21820-51-9 (Phosphotyrosine) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - Animals MH - *Homeostasis MH - Models, Biological MH - Nerve Net/metabolism MH - *Neuronal Plasticity MH - Phosphorylation MH - Phosphotyrosine/*metabolism MH - Protein Tyrosine Phosphatases/*metabolism MH - Rats, Sprague-Dawley MH - Receptors, AMPA/*metabolism MH - Receptors, N-Methyl-D-Aspartate/*metabolism PMC - PMC4578242 EDAT- 2015/09/24 06:00 MHDA- 2016/07/07 06:00 PMCR- 2015/09/22 CRDT- 2015/09/23 06:00 PHST- 2015/04/27 00:00 [received] PHST- 2015/09/14 00:00 [accepted] PHST- 2015/09/23 06:00 [entrez] PHST- 2015/09/24 06:00 [pubmed] PHST- 2016/07/07 06:00 [medline] PHST- 2015/09/22 00:00 [pmc-release] AID - 10.1186/s13041-015-0148-4 [pii] AID - 148 [pii] AID - 10.1186/s13041-015-0148-4 [doi] PST - epublish SO - Mol Brain. 2015 Sep 22;8(1):55. doi: 10.1186/s13041-015-0148-4.