Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Export

@article{citeulike:1362487, abstract = {Learning is accompanied by modulation of postsynaptic signal transduction pathways in neurons. Although the neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) has been implicated in cognitive disorders, its role in learning has been obscured by the perinatal lethality of constitutive knockout mice. Here we report that conditional knockout of Cdk5 in the adult mouse brain improved performance in spatial learning tasks and enhanced hippocampal long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents. Enhanced synaptic plasticity in Cdk5 knockout mice was attributed to reduced NR2B degradation, which caused elevations in total, surface and synaptic NR2B subunit levels and current through NR2B-containing NMDARs. Cdk5 facilitated the degradation of NR2B by directly interacting with both it and its protease, calpain. These findings reveal a previously unknown mechanism by which Cdk5 facilitates calpain-mediated proteolysis of NR2B and may control synaptic plasticity and learning.}, address = {[1] Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, USA. [2] These authors contributed equally to this work.}, author = {Hawasli, Ammar H H. and Benavides, David R R. and Nguyen, Chan and Kansy, Janice W W. and Hayashi, Kanehiro and Chambon, Pierre and Greengard, Paul and Powell, Craig M M. and Cooper, Donald C C. and Bibb, James A A.}, citeulike-article-id = {1362487}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nn1914}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17529984}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17529984}, day = {27}, doi = {10.1038/nn1914}, issn = {1097-6256}, journal = {Nat Neurosci}, keywords = {ca1, ltp}, month = {May}, posted-at = {2007-06-04 12:49:12}, priority = {2}, title = {Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation.}, url = {http://dx.doi.org/10.1038/nn1914}, year = {2007} }

TY - JOUR ID - citeulike:1362487 L3 - citeulike-article-id:1362487 N2 - Learning is accompanied by modulation of postsynaptic signal transduction pathways in neurons. Although the neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) has been implicated in cognitive disorders, its role in learning has been obscured by the perinatal lethality of constitutive knockout mice. Here we report that conditional knockout of Cdk5 in the adult mouse brain improved performance in spatial learning tasks and enhanced hippocampal long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents. Enhanced synaptic plasticity in Cdk5 knockout mice was attributed to reduced NR2B degradation, which caused elevations in total, surface and synaptic NR2B subunit levels and current through NR2B-containing NMDARs. Cdk5 facilitated the degradation of NR2B by directly interacting with both it and its protease, calpain. These findings reveal a previously unknown mechanism by which Cdk5 facilitates calpain-mediated proteolysis of NR2B and may control synaptic plasticity and learning. JF - Nat Neurosci SN - 1097-6256 AD - [1] Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, USA. [2] These authors contributed equally to this work. TI - Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. KW - ca1 KW - ltp AU - Hawasli, Ammar H AU - Benavides, David R AU - Nguyen, Chan AU - Kansy, Janice W AU - Hayashi, Kanehiro AU - Chambon, Pierre AU - Greengard, Paul AU - Powell, Craig M AU - Cooper, Donald C AU - Bibb, James A PY - 2007/05/27/ UR - http://dx.doi.org/10.1038/nn1914 ER -