 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, May 1, 1999, 19(9):3376-3383
Constitutively Active MuSK Is Clustered in the Absence of Agrin and Induces Ectopic Postsynaptic-Like Membranes in Skeletal Muscle Fibers
Graham Jones, Chris Moore, Said Hashemolhosseini, and Hans Rudolf Brenner Department of Physiology, University of Basel, CH-4051 Basel, Switzerland
In skeletal muscle fibers, neural agrin can direct the accumulation of acetylcholine receptors (AChR) and transcription of AChR subunit genes from the subsynaptic nuclei. Although the receptor tyrosine kinase MuSK is required for AChR clustering, it is less clear whether MuSK regulates gene transcription. To elucidate the role of MuSK in these processes, we constructed a constitutively active MuSK receptor, MuSKneuTMuSK, taking advantage of the spontaneous homodimerization of the transmembrane domain of neuT, an oncogenic variant of the neu/erbB2 receptor. In the extrasynaptic region of innervated muscle fibers, MuSKneuTMuSK formed highly concentrated aggregates that colocalized with AChR clusters. Associated with MuSK-induced AChR clusters was a normal complement of synaptic proteins. Moreover, transcription of the AChR-
subunit gene was increased, albeit via an indirect mechanism by MuSK-induced aggregation of erbB receptors and neuregulin. Although neural agrin was not required, the activity of MuSKneuTMuSK was nevertheless potentiated by ectopic expression of a muscle agrin isoform inactive in AChR clustering. To define the role of the kinase domain in the formation of a postsynaptic-like membrane, a second fusion receptor, neuneuTMuSK, which included the MuSK kinase but not the MuSK extracellular domain, was expressed. Significantly, neuneuTMuSK induced AChR clusters that colocalized with aggregates of endogenous MuSK. Taken together, it was concluded that the MuSK kinase domain is sufficient to initiate the recruitment of additional MuSK receptors, which then develop into highly concentrated aggregates by means of a positive feedback loop to induce a postsynaptic membrane in the absence of neural agrin.
Key words: agrin; muscle; MuSK; gene transcription; neuromuscular junction; rat
Copyright © 1999 Society for Neuroscience 0270-6474/99/1993376-08$05.00/0
This article has been cited by other articles:
S. Lin, M. Maj, G. Bezakova, J. P. Magyar, H. R. Brenner, and M. A. Ruegg
Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice
PNAS, August 12, 2008; 105(32): 11406 - 11411.
[Abstract] [Full Text] [PDF]
S. Lin, L. Landmann, M. A. Ruegg, and H. R. Brenner
The Role of Nerve- versus Muscle-Derived Factors in Mammalian Neuromuscular Junction Formation
J. Neurosci., March 26, 2008; 28(13): 3333 - 3340.
[Abstract] [Full Text] [PDF]
Z. Lu, H.-S. Je, P. Young, J. Gross, B. Lu, and G. Feng
Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction
J. Cell Biol., July 30, 2007; 177(6): 1077 - 1089.
[Abstract] [Full Text] [PDF]
J. A. Panzer, Y. Song, and R. J. Balice-Gordon
In Vivo Imaging of Preferential Motor Axon Outgrowth to and Synaptogenesis at Prepatterned Acetylcholine Receptor Clusters in Embryonic Zebrafish Skeletal Muscle
J. Neurosci., January 18, 2006; 26(3): 934 - 947.
[Abstract] [Full Text] [PDF]
A. Jaworski and S. J. Burden
Neuromuscular Synapse Formation in Mice Lacking Motor Neuron- and Skeletal Muscle-Derived Neuregulin-1
J. Neurosci., January 11, 2006; 26(2): 655 - 661.
[Abstract] [Full Text] [PDF]
C. F. Bentzinger, P. Barzaghi, S. Lin, and M. A. Ruegg
Overexpression of mini-agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin-{alpha}2-deficient mice
FASEB J, June 1, 2005; 19(8): 934 - 942.
[Abstract] [Full Text] [PDF]
L. Strochlic, A. Cartaud, A. Mejat, R. Grailhe, L. Schaeffer, J.-P. Changeux, and J. Cartaud
14-3-3 {gamma} associates with muscle specific kinase and regulates synaptic gene transcription at vertebrate neuromuscular synapse
PNAS, December 28, 2004; 101(52): 18189 - 18194.
[Abstract] [Full Text] [PDF]
P. Mittaud, A. A. Camilleri, R. Willmann, S. Erb-Vogtli, S. J. Burden, and C. Fuhrer
A Single Pulse of Agrin Triggers a Pathway That Acts To Cluster Acetylcholine Receptors
Mol. Cell. Biol., September 15, 2004; 24(18): 7841 - 7854.
[Abstract] [Full Text] [PDF]
M. Leu, E. Bellmunt, M. Schwander, I. Farinas, H. R. Brenner, and U. Muller
Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development
Development, June 1, 2003; 130(11): 2291 - 2301.
[Abstract] [Full Text] [PDF]
E. Lacazette, S. Le Calvez, N. Gajendran, and H. R. Brenner
A novel pathway for MuSK to induce key genes in neuromuscular synapse formation
J. Cell Biol., May 26, 2003; 161(4): 727 - 736.
[Abstract] [Full Text] [PDF]
C.-N. Tseng, L. Zhang, M. Cascio, and Z.-Z. Wang
Calcium Plays a Critical Role in Determining the Acetylcholine Receptor-clustering Activities of Alternatively Spliced Isoforms of Agrin
J. Biol. Chem., May 2, 2003; 278(19): 17236 - 17245.
[Abstract] [Full Text] [PDF]
R. Herbst, E. Avetisova, and S. J. Burden
Restoration of synapse formation in Musk mutant mice expressing a Musk/Trk chimeric receptor
Development, January 12, 2002; 129(23): 5449 - 5460.
[Abstract] [Full Text] [PDF]
C. Moore, M. Leu, U. Muller, and H. R. Brenner
Induction of multiple signaling loops by MuSK during neuromuscular synapse formation
PNAS, November 15, 2001; (2001) 251291598.
[Abstract] [Full Text] [PDF]
J. C. Trinidad, G. D. Fischbach, and J. B. Cohen
The Agrin/MuSK Signaling Pathway Is Spatially Segregated from the Neuregulin/ErbB Receptor Signaling Pathway at the Neuromuscular Junction
J. Neurosci., December 1, 2000; 20(23): 8762 - 8770.
[Abstract] [Full Text] [PDF]
A. Briguet and M. A. Ruegg
The Ets Transcription Factor GABP Is Required for Postsynaptic Differentiation In Vivo
J. Neurosci., August 15, 2000; 20(16): 5989 - 5996.
[Abstract] [Full Text] [PDF]
S. G. Rossi, A. E. Vazquez, and R. L. Rotundo
Local Control of Acetylcholinesterase Gene Expression in Multinucleated Skeletal Muscle Fibers: Individual Nuclei Respond to Signals from the Overlying Plasma Membrane
J. Neurosci., February 1, 2000; 20(3): 919 - 928.
[Abstract] [Full Text] [PDF]
M. Tanowitz, J. Si, D.-H. Yu, G.-S. Feng, and L. Mei
Regulation of Neuregulin-Mediated Acetylcholine Receptor Synthesis by Protein Tyrosine Phosphatase SHP2
J. Neurosci., November 1, 1999; 19(21): 9426 - 9435.
[Abstract] [Full Text] [PDF]
H. Zhou, D. J. Glass, G. D. Yancopoulos, and J. R. Sanes
Distinct Domains of MuSK Mediate Its Abilities to Induce and to Associate with Postsynaptic Specializations
J. Cell Biol., September 6, 1999; 146(5): 1133 - 1146.
[Abstract] [Full Text] [PDF]
C. Moore, M. Leu, U. Muller, and H. R. Brenner
Induction of multiple signaling loops by MuSK during neuromuscular synapse formation
PNAS, December 4, 2001; 98(25): 14655 - 14660.
[Abstract] [Full Text] [PDF]
A. Sander, B. A. Hesser, and V. Witzemann
MuSK induces in vivo acetylcholine receptor clusters in a ligand-independent manner
J. Cell Biol., December 24, 2001; 155(7): 1287 - 1296.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|