PMID- 21896318 OWN - NLM STAT- MEDLINE DCOM- 20120120 LR - 20211020 IS - 1872-7972 (Electronic) IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 503 IP - 3 DP - 2011 Oct 10 TI - Developmental localization of NMDA receptors, Src and MAP kinases in mouse brain. PG - 215-9 LID - 10.1016/j.neulet.2011.08.039 [doi] AB - Activation of NMDA receptors (NMDAR) is associated with divergent downstream signaling leading to neuronal survival or death that may be regulated in part by whether the receptor is located synaptically or extrasynaptically. Distinct activation of the MAP kinases ERK and p38 by synaptic and extrasynaptic NMDAR is one of the mechanisms underlying these differences. We have recently shown that the Src family kinases (SFKs) play an important role in neonatal hypoxic-ischemic brain injury by regulating NMDAR phosphorylation. In this study, we characterized the distribution of NMDAR, SFKs and MAP kinases in synaptic and extrasynaptic membrane locations in the postnatal day 7 and adult mouse cortex. We found that the NMDAR, SFKs and phospho-NR2B were predominantly at synapses, whereas striatal-enriched protein tyrosine phosphatase (STEP) and its substrates ERK and p38 were much more concentrated extrasynaptically. NR1/NR2B was the main subunit at extrasynaptic membrane with concomitant NR2B phosphorylation at tyrosine (Y) 1336 in the immature brain. STEP expression increased, while p38 decreased with development in the extrasynaptic membrane. These results suggest that SFKs and STEP are poised to differentially regulate NMDAR-mediated signaling pathways due to their distinct subcellular localization, and thus may contribute to the age-specific differences seen in vulnerability, pathology and consequences of hypoxic-ischemic brain injury. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Jiang, Xiangning AU - Jiang X AD - Department of Neurology, University of California, San Francisco, CA 94143, United States. xiangning.jiang@ucsf.edu FAU - Knox, Renatta AU - Knox R FAU - Pathipati, Praneeti AU - Pathipati P FAU - Ferriero, Donna AU - Ferriero D LA - eng GR - F31 NS073145-01/NS/NINDS NIH HHS/United States GR - R21 NS059613-01A2/NS/NINDS NIH HHS/United States GR - F31 NS073145/NS/NINDS NIH HHS/United States GR - R21 NS059613/NS/NINDS NIH HHS/United States GR - R01 NS33997/NS/NINDS NIH HHS/United States GR - R01 NS033997-14/NS/NINDS NIH HHS/United States GR - R01 NS033997/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110827 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (NR1 NMDA receptor) RN - 0 (NR2B NMDA receptor) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Blotting, Western MH - Brain/*anatomy & histology/*growth & development MH - Brain Chemistry/*physiology MH - Cerebral Cortex/enzymology/growth & development MH - Cytoplasm/enzymology MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/*metabolism MH - Phosphorylation MH - Receptors, N-Methyl-D-Aspartate/drug effects/*metabolism MH - Synapses/enzymology MH - Synaptic Membranes/enzymology MH - p38 Mitogen-Activated Protein Kinases/metabolism MH - src-Family Kinases/*metabolism PMC - PMC3193348 MID - NIHMS325896 EDAT- 2011/09/08 06:00 MHDA- 2012/01/21 06:00 PMCR- 2012/10/10 CRDT- 2011/09/08 06:00 PHST- 2011/07/02 00:00 [received] PHST- 2011/08/15 00:00 [revised] PHST- 2011/08/22 00:00 [accepted] PHST- 2011/09/08 06:00 [entrez] PHST- 2011/09/08 06:00 [pubmed] PHST- 2012/01/21 06:00 [medline] PHST- 2012/10/10 00:00 [pmc-release] AID - S0304-3940(11)01224-9 [pii] AID - 10.1016/j.neulet.2011.08.039 [doi] PST - ppublish SO - Neurosci Lett. 2011 Oct 10;503(3):215-9. doi: 10.1016/j.neulet.2011.08.039. Epub 2011 Aug 27.