 |
 Previous Article | Next Article 
The Journal of Neuroscience, August 15, 1998, 18(16):6340-6348
 -Dystroglycan Functions in Acetylcholine Receptor Aggregation
But Is Not a Coreceptor for Agrin-MuSK Signaling
Christian
Jacobson,
Federica
Montanaro,
Michael
Lindenbaum,
Salvatore
Carbonetto, and
Michael
Ferns
Departments of Biology and Neurology and Neurosurgery, McGill
University and the Centre for Research in Neuroscience,
Montreal, Quebec, H3G 1A4 Canada
 -dystroglycan (-DG) is an agrin-binding protein that
has been implicated in acetylcholine receptor (AChR) clustering, but it
is unclear whether it acts as a coreceptor involved in initial agrin
signaling or as a component involved in later events. To investigate
its role, we have generated antisense derivatives of the C2
mouse muscle cell line, which have reduced -DG expression. When
compared with wild-type cells, the -DG-deficient myotubes have a
dramatic reduction in the number of spontaneous and agrin-induced AChR
clusters. Several findings suggest that this decrease in AChR
clustering is likely not because of a defect in agrin signaling through
the MuSK receptor tyrosine kinase. Compared with wild-type cells, the -DG-deficient cell lines showed only a transient
reduction in the level of agrin-induced MuSK tyrosine phosphorylation
and no reduction in AChR  -subunit tyrosine phosphorylation.
Additionally, agrin-induced phosphorylation of MuSK in wild-type
myotubes was not decreased using agrin fragments that lack the domain
primarily responsible for binding to -DG. Finally, neural
agrin-induced phosphorylation of MuSK was unaffected by treatments such
as excess muscle agrin or anti--DG antibodies, both of which block
agrin--DG binding. Together, these results suggest that -DG is
not required for agrin-MuSK signaling but rather that it may play a
role elsewhere in the clustering pathway, such as in the downstream
consolidation or maintenance of AChR clusters.
Key words:
synaptogenesis; neuromuscular junction; dystroglycan; agrin; acetylcholine receptor; phosphorylation
Copyright © 1998 Society for Neuroscience 0270-6474/98/18166340-09$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. L. Lefebvre, L. Jing, S. Becaficco, C. Franzini-Armstrong, and M. Granato
Differential requirement for MuSK and dystroglycan in generating patterns of neuromuscular innervation
PNAS,
February 13, 2007;
104(7):
2483 - 2488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Tremblay and S. Carbonetto
An Extracellular Pathway for Dystroglycan Function in Acetylcholine Receptor Aggregation and Laminin Deposition in Skeletal Myotubes
J. Biol. Chem.,
May 12, 2006;
281(19):
13365 - 13373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Barresi and K. P. Campbell
Dystroglycan: from biosynthesis to pathogenesis of human disease
J. Cell Sci.,
January 15, 2006;
119(2):
199 - 207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zhang, Y. Wang, Y. Chu, L. Su, Y. Gong, R. Zhang, and S. Xiong
Agrin is involved in lymphocytes activation that is mediated by {alpha}-dystroglycan
FASEB J,
January 1, 2006;
20(1):
50 - 58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. P. Smirnov, P. Barzaghi, K. K. McKee, M. A. Ruegg, and P. D. Yurchenco
Conjugation of LG Domains of Agrins and Perlecan to Polymerizing Laminin-2 Promotes Acetylcholine Receptor Clustering
J. Biol. Chem.,
December 16, 2005;
280(50):
41449 - 41457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Jacobson, D. Duggan, and G. Fischbach
Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle
PNAS,
August 17, 2004;
101(33):
12218 - 12223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. L. McDearmon, A. C. Combs, and J. M. Ervasti
Core 1 Glycans on {alpha}-Dystroglycan Mediate Laminin-induced Acetylcholine Receptor Clustering but Not Laminin Binding
J. Biol. Chem.,
November 7, 2003;
278(45):
44868 - 44873.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Hoover, L. G.W. Hilgenberg, and M. A. Smith
The COOH-terminal domain of agrin signals via a synaptic receptor in central nervous system neurons
J. Cell Biol.,
June 9, 2003;
161(5):
923 - 932.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Parsons, I. Campos, E. M. A. Hirst, and D. L. Stemple
Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos
Development,
March 9, 2003;
129(14):
3505 - 3512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kahl and J. T. Campanelli
A Role for the Juxtamembrane Domain of beta -Dystroglycan in Agrin-Induced Acetylcholine Receptor Clustering
J. Neurosci.,
January 15, 2003;
23(2):
392 - 402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Marangi, S. T. Wieland, and C. Fuhrer
Laminin-1 redistributes postsynaptic proteins and requires rapsyn, tyrosine phosphorylation, and Src and Fyn to stably cluster acetylcholine receptors
J. Cell Biol.,
May 28, 2002;
157(5):
883 - 895.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.K. Hayashi, M. Ogawa, K. Tagawa, S. Noguchi, T. Ishihara, I. Nonaka, and a. K. Arahata
Selective deficiency of {{alpha}}-dystroglycan in Fukuyama-type congenital muscular dystrophy
Neurology,
July 10, 2001;
57(1):
115 - 121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Borges and M. Ferns
Agrin-induced Phosphorylation of the Acetylcholine Receptor Regulates Cytoskeletal Anchoring and Clustering
J. Cell Biol.,
March 26, 2001;
153(1):
1 - 12.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Jacobson, P. D. Cote, S. G. Rossi, R. L. Rotundo, and S. Carbonetto
The Dystroglycan Complex Is Necessary for Stabilization of Acetylcholine Receptor Clusters at Neuromuscular Junctions and Formation of the Synaptic Basement Membrane
J. Cell Biol.,
January 29, 2001;
152(3):
435 - 450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Bowe, D. B. Mendis, and J. R. Fallon
The Small Leucine-rich Repeat Proteoglycan Biglycan Binds to {alpha}-Dystroglycan and Is Upregulated in Dystrophic Muscle
J. Cell Biol.,
February 21, 2000;
148(4):
801 - 810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Durbeej and K. P. Campbell
Biochemical Characterization of the Epithelial Dystroglycan Complex
J. Biol. Chem.,
September 10, 1999;
274(37):
26609 - 26616.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. G. W. Hilgenberg, C. L. Hoover, and M. A. Smith
Evidence of an Agrin Receptor in Cortical Neurons
J. Neurosci.,
September 1, 1999;
19(17):
7384 - 7393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Montanaro, M. Lindenbaum, and S. Carbonetto
alpha -Dystroglycan Is a Laminin Receptor Involved in Extracellular Matrix Assembly on Myotubes and Muscle Cell Viability
J. Cell Biol.,
June 14, 1999;
145(6):
1325 - 1340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Jones, C. Moore, S. Hashemolhosseini, and H. R. Brenner
Constitutively Active MuSK Is Clustered in the Absence of Agrin and Induces Ectopic Postsynaptic-Like Membranes in Skeletal Muscle Fibers
J. Neurosci.,
May 1, 1999;
19(9):
3376 - 3383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
