Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity. Export

@article{citeulike:1019527, abstract = {Bidirectional changes in the efficacy of neuronal synaptic transmission, such as hippocampal long-term potentiation (LTP) and long-term depression (LTD), are thought to be mechanisms for information storage in the brain. LTP and LTD may be mediated by the modulation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazloe proprionic acid) receptor phosphorylation. Here we show that LTP and LTD reversibly modify the phosphorylation of the AMPA receptor GluR1 subunit. However, contrary to the hypothesis that LTP and LTD are the functional inverse of each other, we find that they are associated with phosphorylation and dephosphorylation, respectively, of distinct GluR1 phosphorylation sites. Moreover, the site modulated depends on the stimulation history of the synapse. LTD induction in naive synapses dephosphorylates the major cyclic-AMP-dependent protein kinase (PKA) site, whereas in potentiated synapses the major calcium/calmodulin-dependent protein kinase II (CaMKII) site is dephosphorylated. Conversely, LTP induction in naive synapses and depressed synapses increases phosphorylation of the CaMKII site and the PKA site, respectively. LTP is differentially sensitive to CaMKII and PKA inhibitors depending on the history of the synapse. These results indicate that AMPA receptor phosphorylation is critical for synaptic plasticity, and that identical stimulation conditions recruit different signal-transduction pathways depending on synaptic history.}, address = {Howard Hughes Medical Institute, Department of Neuroscience, Johns Hopkins Medical School, Baltimore, Maryland, USA.}, author = {Lee, H. K. and Barbarosie, M. and Kameyama, K. and Bear, M. F. and Huganir, R. L.}, citeulike-article-id = {1019527}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/35016089}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/10879537}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=10879537}, day = {22}, doi = {10.1038/35016089}, issn = {0028-0836}, journal = {Nature}, keywords = {ampar\_p, ca1, kt, pka}, month = {June}, number = {6789}, pages = {955--959}, posted-at = {2006-12-30 03:29:39}, priority = {2}, title = {Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity.}, url = {http://dx.doi.org/10.1038/35016089}, volume = {405}, year = {2000} }

TY - JOUR ID - citeulike:1019527 L3 - citeulike-article-id:1019527 N2 - Bidirectional changes in the efficacy of neuronal synaptic transmission, such as hippocampal long-term potentiation (LTP) and long-term depression (LTD), are thought to be mechanisms for information storage in the brain. LTP and LTD may be mediated by the modulation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazloe proprionic acid) receptor phosphorylation. Here we show that LTP and LTD reversibly modify the phosphorylation of the AMPA receptor GluR1 subunit. However, contrary to the hypothesis that LTP and LTD are the functional inverse of each other, we find that they are associated with phosphorylation and dephosphorylation, respectively, of distinct GluR1 phosphorylation sites. Moreover, the site modulated depends on the stimulation history of the synapse. LTD induction in naive synapses dephosphorylates the major cyclic-AMP-dependent protein kinase (PKA) site, whereas in potentiated synapses the major calcium/calmodulin-dependent protein kinase II (CaMKII) site is dephosphorylated. Conversely, LTP induction in naive synapses and depressed synapses increases phosphorylation of the CaMKII site and the PKA site, respectively. LTP is differentially sensitive to CaMKII and PKA inhibitors depending on the history of the synapse. These results indicate that AMPA receptor phosphorylation is critical for synaptic plasticity, and that identical stimulation conditions recruit different signal-transduction pathways depending on synaptic history. IS - 6789 JF - Nature SN - 0028-0836 AD - Howard Hughes Medical Institute, Department of Neuroscience, Johns Hopkins Medical School, Baltimore, Maryland, USA. EP - 959 TI - Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity. VL - 405 SP - 955 KW - ampar_p KW - ca1 KW - kt KW - pka AU - Lee, HK AU - Barbarosie, M AU - Kameyama, K AU - Bear, MF AU - Huganir, RL PY - 2000/06/22/ UR - http://dx.doi.org/10.1038/35016089 ER -