Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

J. Neurosci. 29 (14): 4498-4511

Copyright © 2009 by the Society for Neuroscience.

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

Abstract: 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 for publication Dec. 22, 2008. Revision received Feb. 27, 2009. Accepted for publication 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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
PMCA2 via PSD-95 Controls Calcium Signaling by {alpha}7-Containing Nicotinic Acetylcholine Receptors on Aspiny Interneurons.
D. Gomez-Varela, M. Schmidt, J. Schoellerman, E. C. Peters, and D. K. Berg (2012)
J. Neurosci. 32, 6894-6905
   Abstract »    Full Text »    PDF »
Parasynaptic NMDA Receptor Signaling Couples Neuronal Glutamate Transporter Function to AMPA Receptor Synaptic Distribution and Stability.
L. A. Jarzylo and H.-Y. Man (2012)
J. Neurosci. 32, 2552-2563
   Abstract »    Full Text »    PDF »
Na+, K+-ATPase: Functions in the nervous system and involvement in neurologic disease.
E. E. Benarroch (2011)
Neurology 76, 287-293
   Full Text »    PDF »
Regional aerobic glycolysis in the human brain.
S. N. Vaishnavi, A. G. Vlassenko, M. M. Rundle, A. Z. Snyder, M. A. Mintun, and M. E. Raichle (2010)
PNAS 107, 17757-17762
   Abstract »    Full Text »    PDF »
Spatial correlation between brain aerobic glycolysis and amyloid-{beta} (A{beta}) deposition.
A. G. Vlassenko, S. N. Vaishnavi, L. Couture, D. Sacco, B. J. Shannon, R. H. Mach, J. C. Morris, M. E. Raichle, and M. A. Mintun (2010)
PNAS 107, 17763-17767
   Abstract »    Full Text »    PDF »
RNG105 Deficiency Impairs the Dendritic Localization of mRNAs for Na+/K+ ATPase Subunit Isoforms and Leads to the Degeneration of Neuronal Networks.
N. Shiina, K. Yamaguchi, and M. Tokunaga (2010)
J. Neurosci. 30, 12816-12830
   Abstract »    Full Text »    PDF »
Glutamate Transporter Coupling to Na,K-ATPase.
E. M. Rose, J. C. P. Koo, J. E. Antflick, S. M. Ahmed, S. Angers, and D. R. Hampson (2009)
J. Neurosci. 29, 8143-8155
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882