PMID- 21600287 OWN - NLM STAT- MEDLINE DCOM- 20120227 LR - 20111031 IS - 1095-9327 (Electronic) IS - 1044-7431 (Linking) VI - 48 IP - 4 DP - 2011 Dec TI - Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function. PG - 308-20 LID - 10.1016/j.mcn.2011.05.001 [doi] AB - Research over the last few decades has shaped our understanding of the crucial involvement of the N-methyl-D-aspartate receptor (NMDAR) in mediating excitatory synaptic neurotransmission, neuronal development and learning and memory. The complexity of NMDAR modulation has escalated with the knowledge that receptors can traffic between synaptic and extrasynaptic sites, and that location on the plasma membrane profoundly affects the physiological function of NMDARs. Moreover, mechanisms that regulate NMDAR subcellular localization and function, such as protein-protein interactions, phosphorylation, palmitoylation, ubiquitination and receptor proteolytic cleavage, may differ for synaptic and extrasynaptic NMDARs. Recent studies suggest that NMDAR mislocalization is a dominant contributing factor to glutamatergic dysfunction and pathogenesis in neurological disorders such as Huntington's disease, Alzheimer's disease and ischemia. Therapeutic approaches that specifically rectify receptor mislocalization or target resulting downstream apoptotic signaling could be beneficial for preventing disease onset or progression across many disorders that are commonly caused by NMDAR dysfunction. This review will summarize the molecular mechanisms that regulate synaptic and extrasynaptic NMDAR localization in both physiologic and pathogenic states. CI - Copyright A(c) 2011 Elsevier Inc. All rights reserved. FAU - Gladding, Clare M AU - Gladding CM AD - Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. clareg@interchange.ubc.ca FAU - Raymond, Lynn A AU - Raymond LA LA - eng PT - Journal Article PT - Review DEP - 20110507 PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Animals MH - Models, Biological MH - Receptors, N-Methyl-D-Aspartate/*physiology MH - Signal Transduction/*physiology MH - Synapses/*physiology MH - Synaptic Transmission/*physiology EDAT- 2011/05/24 06:00 MHDA- 2012/03/01 06:00 CRDT- 2011/05/24 06:00 PHST- 2011/03/01 00:00 [received] PHST- 2011/04/20 00:00 [revised] PHST- 2011/05/01 00:00 [accepted] PHST- 2011/05/24 06:00 [entrez] PHST- 2011/05/24 06:00 [pubmed] PHST- 2012/03/01 06:00 [medline] AID - S1044-7431(11)00107-2 [pii] AID - 10.1016/j.mcn.2011.05.001 [doi] PST - ppublish SO - Mol Cell Neurosci. 2011 Dec;48(4):308-20. doi: 10.1016/j.mcn.2011.05.001. Epub 2011 May 7.