title: Developmental localization of NMDA receptors, Src and MAP kinases in mouse brain.
abstract: 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.
authors: Department of Neurology, University of California, San Francisco, CA 94143, United States. xiangning.jiang@ucsf.edu
authors: Xiangning
authors: X
authors: Jiang
authors: Renatta
authors: R
authors: Knox
authors: Praneeti
authors: P
authors: Pathipati
authors: Donna
authors: D
authors: Ferriero
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000033:anatomy & histology* / Q000254:growth & development*; D001923:Brain Chemistry / Q000502:physiology*; D002540:Cerebral Cortex / Q000201:enzymology / Q000254:growth & development; D003593:Cytoplasm / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology; D013570:Synaptic Membranes / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases