 |
 Previous Article | Next Article 
The Journal of Neuroscience, January 15, 2001, 21(2):504-512
Membrane Lipid Rafts Are Necessary for the Maintenance of the
 7 Nicotinic Acetylcholine Receptor in Somatic Spines of Ciliary
Neurons
Juan L.
Brusés,
Norbert
Chauvet, and
Urs
Rutishauser
Cellular Biochemistry and Biophysics Program, Memorial
Sloan-Kettering Cancer Center, New York, New York 10021
Calcium-permeable neurotransmitter receptors are concentrated into
structurally and biochemically isolated cellular compartments to
localize calcium-mediated events during neurotransmission. The
cytoplasmic membrane contains lipid microdomains called lipid rafts,
which can gather into microscopically visible clusters, and thus the
association of a particular protein with lipid rafts can result in its
redistribution on the cell surface. The present study asks whether
lipid rafts participate in the formation and maintenance of the
calcium-permeable  7-subunit nicotinic acetylcholine receptor
(7nAChR) clusters found in somatic spines of ciliary neurons. Lipid
rafts and 7nAChR become progressively colocalized within somatic
spines during synaptogenesis. To determine whether these rafts are
required for the maintenance of 7nAChR aggregates, cholesterol was
extracted from dissociated ciliary neurons by treatment with
methyl- -cyclodextrin. This treatment caused the dispersion of lipid
rafts and the redistribution of 7nAChR into small clusters over the
cell surface, suggesting that the integrity of lipid rafts is required
to maintain the receptor clustering. However, lipid raft dispersion
also caused the depolymerization of the F-actin cytoskeleton, which can
also tether the receptor at specific sites. To assess whether
interaction between rafts and 7nAChR is independent of F-actin
filaments, the lipid raft patches were stabilized with a combination of
the cholera toxin B subunit (CTX), which specifically binds to the raft
component ganglioside GM1, and an antibody against CTX. The
stabilized rafts were then treated with latrunculin-A to depolymerize
F-actin. Under these conditions, large patches of CTX persisted and
were colocalized with 7nAChR, indicating that the aggregates of
receptors can be maintained independently of the underlying F-actin
cytoskeleton. Moreover, it was found that the 7nAChR is resistant to
detergent extraction at 4°C and floats with the caveolin-containing
lipid-rich fraction during density gradient centrifugation, properties
that are consistent with a direct association between the receptor and
the membrane microdomains.
Key words:
ciliary ganglion; somatic spines; lipid rafts; 7
nicotinic acetylcholine receptor; receptor clusters; actin
cytoskeleton; synapse formation
Copyright © 2001 Society for Neuroscience 0270-6474/01/212504-09$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. E. Baenziger, S. E. Ryan, M. M. Goodreid, N. Q. Vuong, R. M. Sturgeon, and C. J. B. daCosta
Lipid Composition Alters Drug Action at the Nicotinic Acetylcholine Receptor
Mol. Pharmacol.,
March 1, 2008;
73(3):
880 - 890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Stetzkowski-Marden, K. Gaus, M. Recouvreur, A. Cartaud, and J. Cartaud
Agrin elicits membrane lipid condensation at sites of acetylcholine receptor clusters in C2C12 myotubes
J. Lipid Res.,
October 1, 2006;
47(10):
2121 - 2133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zhu, W. C. Xiong, and L. Mei
Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering.
J. Neurosci.,
May 3, 2006;
26(18):
4841 - 4851.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Chen, S. Chi, M. Liu, W. Yang, T. Wei, Z. Qi, and F. Yang
Inhibitory effect of ganglioside GD1b on K+ current in hippocampal neurons and its involvement in apoptosis suppression
J. Lipid Res.,
December 1, 2005;
46(12):
2580 - 2585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Eisensamer, M. Uhr, S. Meyr, G. Gimpl, T. Deiml, G. Rammes, J. J. Lambert, W. Zieglgansberger, F. Holsboer, and R. Rupprecht
Antidepressants and Antipsychotic Drugs Colocalize with 5-HT3 Receptors in Raft-Like Domains
J. Neurosci.,
November 2, 2005;
25(44):
10198 - 10206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Kumar and S. Meizel
Nicotinic Acetylcholine Receptor Subunits and Associated Proteins in Human Sperm
J. Biol. Chem.,
July 8, 2005;
280(27):
25928 - 25935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-H. Cho, W. Song, K. Leitzell, E. Teo, A. D. Meleth, M. W. Quick, and R. A. J. Lester
Rapid Upregulation of {alpha}7 Nicotinic Acetylcholine Receptors by Tyrosine Dephosphorylation
J. Neurosci.,
April 6, 2005;
25(14):
3712 - 3723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Liu, A. W. Tearle, Q. Nai, and D. K. Berg
Rapid Activity-Driven SNARE-Dependent Trafficking of Nicotinic Receptors on Somatic Spines
J. Neurosci.,
February 2, 2005;
25(5):
1159 - 1168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Alldred, J. Mulder-Rosi, S. E. Lingenfelter, G. Chen, and B. Luscher
Distinct {gamma}2 Subunit Domains Mediate Clustering and Synaptic Function of Postsynaptic GABAA Receptors and Gephyrin
J. Neurosci.,
January 19, 2005;
25(3):
594 - 603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C. Drisdel, E. Manzana, and W. N. Green
The Role of Palmitoylation in Functional Expression of Nicotinic {alpha}7 Receptors
J. Neurosci.,
November 17, 2004;
24(46):
10502 - 10510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Badizadegan, H. E. Wheeler, Y. Fujinaga, and W. I. Lencer
Trafficking of cholera toxin-ganglioside GM1 complex into Golgi and induction of toxicity depend on actin cytoskeleton
Am J Physiol Cell Physiol,
November 1, 2004;
287(5):
C1453 - C1462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Musch, D.-L. T. Koomoa, and L. Goldstein
Hypotonicity-induced Exocytosis of the Skate Anion Exchanger skAE1: ROLE OF LIPID RAFT REGIONS
J. Biol. Chem.,
September 17, 2004;
279(38):
39447 - 39453.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Rohrbough, E. Rushton, L. Palanker, E. Woodruff, H. J. G. Matthies, U. Acharya, J. K. Acharya, and K. Broadie
Ceramidase Regulates Synaptic Vesicle Exocytosis and Trafficking
J. Neurosci.,
September 8, 2004;
24(36):
7789 - 7803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. R. Butchbach, G. Tian, H. Guo, and C.-l. G. Lin
Association of Excitatory Amino Acid Transporters, Especially EAAT2, with Cholesterol-rich Lipid Raft Microdomains: IMPORTANCE FOR EXCITATORY AMINO ACID TRANSPORTER LOCALIZATION AND FUNCTION
J. Biol. Chem.,
August 13, 2004;
279(33):
34388 - 34396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. B. daCosta, I. D. Wagg, M. E. McKay, and J. E. Baenziger
Phosphatidic Acid and Phosphatidylserine Have Distinct Structural and Functional Interactions with the Nicotinic Acetylcholine Receptor
J. Biol. Chem.,
April 9, 2004;
279(15):
14967 - 14974.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Gong, L. Chang, K. L. Viola, P. N. Lacor, M. P Lambert, C. E. Finch, G. A. Krafft, and W. L. Klein
Alzheimer's disease-affected brain: Presence of oligomeric A{beta} ligands (ADDLs) suggests a molecular basis for reversible memory loss
PNAS,
September 2, 2003;
100(18):
10417 - 10422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Oshikawa, Y. Toya, T. Fujita, M. Egawa, J. Kawabe, S. Umemura, and Y. Ishikawa
Nicotinic acetylcholine receptor {alpha}7 regulates cAMP signal within lipid rafts
Am J Physiol Cell Physiol,
September 1, 2003;
285(3):
C567 - C574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hering, C.-C. Lin, and M. Sheng
Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and Surface AMPA Receptor Stability
J. Neurosci.,
April 15, 2003;
23(8):
3262 - 3271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Nakai and H. Kamiguchi
Migration of nerve growth cones requires detergent-resistant membranes in a spatially defined and substrate-dependent manner
J. Cell Biol.,
December 23, 2002;
159(6):
1097 - 1108.
[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]
|
|
|
|
|
|
|
D. Konno, J.-A. Ko, S. Usui, K. Hori, H. Maruoka, M. Inui, T. Fujikado, Y. Tano, T. Suzuki, K. Tohyama, et al.
The postsynaptic density and dendritic raft localization of PSD-Zip70, which contains an N-myristoylation sequence and leucine-zipper motifs
J. Cell Sci.,
January 12, 2002;
115(23):
4695 - 4706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Morris
Mechanosensitive Membrane Traffic and an Optimal Strategy for Volume and Surface Area Regulation in CNS Neurons
Integr. Comp. Biol.,
August 1, 2001;
41(4):
721 - 727.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
