WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (45)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Trinidad, J. C.
Right arrow Articles by Cohen, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Trinidad, J. C.
Right arrow Articles by Cohen, J. B.

 Previous Article  |  Next Article 

The Journal of Neuroscience, December 1, 2000, 20(23):8762-8770

The Agrin/MuSK Signaling Pathway Is Spatially Segregated from the Neuregulin/ErbB Receptor Signaling Pathway at the Neuromuscular Junction

Jonathan C. Trinidad1, Gerald D. Fischbach2, and Jonathan B. Cohen1

1 Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, and 2 National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892

The neuregulin/erbB receptor and agrin/MuSK pathways are critical for communication between the nerve, muscle, and Schwann cell that establishes the precise topological arrangement at the vertebrate neuromuscular junction (NMJ). ErbB2, erbB3, and erbB4 as well as neuregulin, agrin, and MuSK are known to be concentrated at the NMJ. Here we have examined NMJs from gastrocnemius muscle of adult rat using immunofluorescence confocal microscopy to characterize in detail the distribution of these proteins relative to the distribution of acetylcholine receptors (AChRs). We have determined that erbB2 and erbB4 are enriched in the depths of the secondary junctional folds on the postsynaptic muscle membrane. In contrast, erbB3 at the NMJ was concentrated at presynaptic terminal Schwann cells. This distribution strongly argues that erbB2/erbB4 heterodimers are the functional postsynaptic neuregulin receptors of the NMJ. Neuregulin was localized to the axon terminal, secondary folds, and terminal Schwann cells, where it was in a position to signal through erbB receptors. MuSK was concentrated in the postsynaptic primary gutter region where it was codistributed with AChRs. Agrin was present at the axon terminal and in the basal lamina associated with the primary gutter region, but not in the secondary junctional folds. The differential distributions of the neuregulin and agrin signaling pathways argue against neuregulin and erbB receptors being localized to the NMJ via direct interactions with either agrin or MuSK.

Key words: neuregulin; erbB receptor; agrin; MuSK; neuromuscular junction; immunohistochemistry

Copyright © 2000 Society for Neuroscience  0270-6474/00/20238762-09$05.00/0


This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
F. A. Court, T. H. Gillingwater, S. Melrose, D. L. Sherman, K. N. Greenshields, A. J. Morton, J. B. Harris, H. J. Willison, and R. R. Ribchester
Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions
J. Cell Sci., December 1, 2008; 121(23): 3901 - 3911.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
C. B. Mantilla and G. C. Sieck
Key aspects of phrenic motoneuron and diaphragm muscle development during the perinatal period
J Appl Physiol, June 1, 2008; 104(6): 1818 - 1827.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. D. Weatherbee, K. V. Anderson, and L. A. Niswander
LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction.
Development, December 1, 2006; 133(24): 4993 - 5000.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
N. J. Hellyer, C. B. Mantilla, E. W. Park, W.-Z. Zhan, and G. C. Sieck
Neuregulin-dependent protein synthesis in C2C12 myotubes and rat diaphragm muscle
Am J Physiol Cell Physiol, November 1, 2006; 291(5): C1056 - C1061.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. R. Hayworth, S. E. Moody, L. A. Chodosh, P. Krieg, M. Rimer, and W. J. Thompson
Induction of neuregulin signaling in mouse schwann cells in vivo mimics responses to denervation.
J. Neurosci., June 21, 2006; 26(25): 6873 - 6884.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. K. Y. Fu, F. C. F. Ip, W.-Y. Fu, J. Cheung, J. H. Wang, W.-H. Yung, and N. Y. Ip
Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice
PNAS, October 18, 2005; 102(42): 15224 - 15230.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
F. Chevessier, B. Faraut, A. Ravel-Chapuis, P. Richard, K. Gaudon, S. Bauche, C. Prioleau, R. Herbst, E. Goillot, C. Ioos, et al.
MUSK, a new target for mutations causing congenital myasthenic syndrome
Hum. Mol. Genet., December 15, 2004; 13(24): 3229 - 3240.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. Cartaud, L. Strochlic, M. Guerra, B. Blanchard, M. Lambergeon, E. Krejci, J. Cartaud, and C. Legay
MuSK is required for anchoring acetylcholinesterase at the neuromuscular junction
J. Cell Biol., May 24, 2004; 165(4): 505 - 515.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Canto, E. Suarez, J. M. Lizcano, E. Grino, P. R. Shepherd, L. G. D. Fryer, D. Carling, J. Bertran, M. Palacin, A. Zorzano, et al.
Neuregulin Signaling on Glucose Transport in Muscle Cells
J. Biol. Chem., March 26, 2004; 279(13): 12260 - 12268.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
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]

Home page
 IOVSHome page
S. Khanna, C. R. Richmonds, H. J. Kaminski, and J. D. Porter
Molecular Organization of the Extraocular Muscle Neuromuscular Junction: Partial Conservation of and Divergence from the Skeletal Muscle Prototype
Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 1918 - 1926.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
N. K. Lebrasseur, G. M. Cote, T. A. Miller, R. A. Fielding, and D. B. Sawyer
Regulation of neuregulin/ErbB signaling by contractile activity in skeletal muscle
Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1149 - C1155.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Ma, Y. Z. Huang, G. M. Pitcher, J. G. Valtschanoff, Y. H. Ma, L. Y. Feng, B. Lu, W. C. Xiong, M. W. Salter, R. J. Weinberg, et al.
Ligand-Dependent Recruitment of the ErbB4 Signaling Complex into Neuronal Lipid Rafts
J. Neurosci., April 15, 2003; 23(8): 3164 - 3175.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Y. Liu, B. Ford, M. A. Mann, and G. D. Fischbach
Neuregulins Increase {alpha}7 Nicotinic Acetylcholine Receptors and Enhance Excitatory Synaptic Transmission in GABAergic Interneurons of the Hippocampus
J. Neurosci., August 1, 2001; 21(15): 5660 - 5669.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Z. Huang, Q. Wang, W. C. Xiong, and L. Mei
Erbin Is a Protein Concentrated at Postsynaptic Membranes That Interacts with PSD-95
J. Biol. Chem., May 25, 2001; 276(22): 19318 - 19326.
[Abstract] [Full Text] [PDF]


-
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-