The Journal of Neuroscience, April 8, 2009, 29(14):4498-4511; doi:10.1523/JNEUROSCI.6094-08.2009
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Cellular/Molecular
Na,K-ATPase Activity Regulates AMPA Receptor Turnover through Proteasome-Mediated Proteolysis
Dawei Zhang,1
Qingming Hou,1
Min Wang,2
Amy Lin,1
Larissa Jarzylo,1
Allison Navis,1
Aram Raissi,1
Fang Liu,2 and
Heng-Ye Man1
1Department of Biology, Boston University, Boston, Massachusetts 02215, and 2Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, Ontario, Canada M5T 1R8
Correspondence should be addressed to Heng-Ye Man, Department of Biology, Boston University, 24 Cummington Street, Boston, MA 02215. Email: hman{at}bu.edu
Neuronal activity largely depends on two key components on the membrane: the Na,K-ATPase (NKA) that maintains the ion gradients and sets the foundation of excitability, and the ionotropic glutamatergic AMPA receptors (AMPARs) through which sodium influx forms the driving force for excitation. Because the frequent sodium transients from glutamate receptor activity need to be efficiently extruded, a functional coupling between NKA and AMPARs should be a necessary cellular device for synapse physiology. We show that NKA is enriched at synapses and associates with AMPARs. NKA dysfunction induces a rapid reduction in AMPAR cell-surface expression as well as total protein abundance, leading to a long-lasting depression in synaptic transmission. AMPAR proteolysis requires sodium influx, proteasomal activity and receptor internalization. These data elucidate a novel mechanism by which NKA regulates AMPAR turnover and thereby synaptic strength and brain function.
Received Dec. 22, 2008;
revised Feb. 27, 2009;
accepted March 9, 2009.
Correspondence should be addressed to Heng-Ye Man, Department of Biology, Boston University, 24 Cummington Street, Boston, MA 02215. Email: hman{at}bu.edu
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E. M. Rose, J. C. P. Koo, J. E. Antflick, S. M. Ahmed, S. Angers, and D. R. Hampson
Glutamate Transporter Coupling to Na,K-ATPase
J. Neurosci.,
June 24, 2009;
29(25):
8143 - 8155.
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