 |
 Previous Article | Next Article 
The Journal of Neuroscience, March 15, 1999, 19(6):1998-2007
Metabolic Stabilization of Muscle Nicotinic Acetylcholine
Receptor by Rapsyn
Zuo-Zhong
Wang1,
Askale
Mathias1,
Medha
Gautam2, and
Zach W.
Hall1
1 Laboratory of Cell Biology, National Institute of
Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and 2 Department of Pharmacological and Physiological
Science, St. Louis University Medical School, St. Louis, Missouri
63104
Although the metabolic half-life of muscle endplate acetylcholine
receptor (AChR) changes during development and after denervation in the
adult, little is known about the molecular mechanisms that influence
receptor stability. We have investigated the effect on AChR turnover of
its interaction with rapsyn, a 43 kDa peripheral membrane protein that
is closely associated with the AChR in muscle cells and is required for
its clustering at endplates. Both in transfected COS cells and in
cultured myotubes from rapsyn-negative and rapsyn-positive mice, we
have found that the presence of rapsyn slows the turnover of AChRs by
as much as twofold. The effect was similar for both embryonic
( 2   ) and adult (2 ) AChRs and for AChRs whose subunit lacked a putative tyrosine
phosphorylation site. Neither colchicine nor cytochalasin D altered
AChR turnover or prevented the rapsyn effect. Mutant rapsyn proteins
whose N-terminal myristoylation signal was eliminated, or whose C
terminus or zinc-finger domains were deleted, failed to change the rate
of receptor turnover. Each of these mutations affects the association
of the AChR with rapsyn, suggesting that AChR stability is altered by
interaction between the two proteins. Our results suggest that, in
addition to its role in AChR clustering, rapsyn also functions to
metabolically stabilize the AChR.
Key words:
nicotinic receptors; rapsyn; 43 kDa protein; receptor
turnover; acetylcholine; neuromuscular junction; endplate; myotubes
Copyright © 1999 Society for Neuroscience 0270-6474/99/1961998-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
E. G. Bruneau, J. A. Esteban, and M. Akaaboune
Receptor-associated proteins and synaptic plasticity
FASEB J,
March 1, 2009;
23(3):
679 - 688.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wang, N.-J. Ruan, L. Qian, W.-l. Lei, F. Chen, and Z.-G. Luo
Wnt/{beta}-Catenin Signaling Suppresses Rapsyn Expression and Inhibits Acetylcholine Receptor Clustering at the Neuromuscular Junction
J. Biol. Chem.,
August 1, 2008;
283(31):
21668 - 21675.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Martinez-Martinez, M. Losen, H. Duimel, P. Frederik, F. Spaans, P. Molenaar, A. Vincent, and M. H. De Baets
Overexpression of Rapsyn in Rat Muscle Increases Acetylcholine Receptor Levels in Chronic Experimental Autoimmune Myasthenia Gravis
Am. J. Pathol.,
February 1, 2007;
170(2):
644 - 657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cossins, G. Burke, S. Maxwell, H. Spearman, S. Man, J. Kuks, A. Vincent, J. Palace, C. Fuhrer, and D. Beeson
Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations
Brain,
October 1, 2006;
129(10):
2773 - 2783.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Dai, W. C. Xiong, and L. Mei
Erbin Inhibits RAF Activation by Disrupting the Sur-8-Ras-Raf Complex
J. Biol. Chem.,
January 13, 2006;
281(2):
927 - 933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Losen, M. H. W. Stassen, P. Martinez-Martinez, B. M. Machiels, H. Duimel, P. Frederik, H. Veldman, J. H. J. Wokke, F. Spaans, A. Vincent, et al.
Increased expression of rapsyn in muscles prevents acetylcholine receptor loss in experimental autoimmune myasthenia gravis
Brain,
October 1, 2005;
128(10):
2327 - 2337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. L Gervasio and W. D Phillips
Increased ratio of rapsyn to ACh receptor stabilizes postsynaptic receptors at the mouse neuromuscular synapse
J. Physiol.,
February 1, 2005;
562(3):
673 - 685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Raouf, Y. Chakfe, D. Blais, A. Speelman, E. Boue-Grabot, D. Henderson, and P. Seguela
Selective Knock-Down of P2X7 ATP Receptor Function by Dominant-Negative Subunits
Mol. Pharmacol.,
March 1, 2004;
65(3):
646 - 654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Marchand, A. Devillers-Thiery, S. Pons, J.-P. Changeux, and J. Cartaud
Rapsyn Escorts the Nicotinic Acetylcholine Receptor Along the Exocytic Pathway via Association with Lipid Rafts
J. Neurosci.,
October 15, 2002;
22(20):
8891 - 8901.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ango, J.-P. Pin, J. C. Tu, B. Xiao, P. F. Worley, J. Bockaert, and L. Fagni
Dendritic and Axonal Targeting of Type 5 Metabotropic Glutamate Receptor Is Regulated by Homer1 Proteins and Neuronal Excitation
J. Neurosci.,
December 1, 2000;
20(23):
8710 - 8716.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. Waggoner, K. A. Dickinson, D. S. Poole, Y. Tabuse, J. Miwa, and W. R. Schafer
Long-Term Nicotine Adaptation in Caenorhabditis elegans Involves PKC-Dependent Changes in Nicotinic Receptor Abundance
J. Neurosci.,
December 1, 2000;
20(23):
8802 - 8811.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-O. NGHIÊM, L. BETTENDORFF, and J.-P. CHANGEUX
Specific phosphorylation of Torpedo 43K rapsyn by endogenous kinase(s) with thiamine triphosphate as the phosphate donor
FASEB J,
March 1, 2000;
14(3):
543 - 554.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. G. M. Jugloff, R. Khanna, L. C. Schlichter, and O. T. Jones
Internalization of the Kv1.4 Potassium Channel Is Suppressed by Clustering Interactions with PSD-95
J. Biol. Chem.,
January 14, 2000;
275(2):
1357 - 1364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
