Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 706K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Deconinck, A. E. Articles by Davies, K. E. Search for Related Content PubMed Articles by Deconinck, A. E. Articles by Davies, K. E. Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/1997//883 $5.00
The Journal of Cell Biology, Volume 136, Number 4, , 1997 883-894

Postsynaptic Abnormalities at the Neuromuscular Junctions of Utrophin-deficient Mice

Anne E. Deconinck^*, Allyson C. Potter^*, Jonathon M. Tinsley^*, Sarah J. Wood, Ruth Vater, Carol Young, Laurent Metzinger^*, Angela Vincent, Clarke R. Slater, and Kay E. Davies^*

^* Laboratory of Genetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom; School of Neurosciences, University of Newcastle upon Tyne and Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, United Kingdom; and Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9QU, United Kingdom

Utrophin is a dystrophin-related cytoskeletal protein expressed in many tissues. It is thought to link F-actin in the internal cytoskeleton to a transmembrane protein complex similar to the dystrophin protein complex (DPC). At the adult neuromuscular junction (NMJ), utrophin is precisely colocalized with acetylcholine receptors (AChRs) and recent studies have suggested a role for utrophin in AChR cluster formation or maintenance during NMJ differentiation. We have disrupted utrophin expression by gene targeting in the mouse. Such mice have no utrophin detectable by Western blotting or immunocytochemistry. Utrophindeficient mice are healthy and show no signs of weakness. However, their NMJs have reduced numbers of AChRs (-bungarotoxin [-BgTx] binding reduced to 60% normal) and decreased postsynaptic folding, though only minimal electrophysiological changes. Utrophin is thus not essential for AChR clustering at the NMJ but may act as a component of the postsynaptic cytoskeleton, contributing to the development or maintenance of the postsynaptic folds. Defects of utrophin could underlie some forms of congenital myasthenic syndrome in which a reduction of postsynaptic folds is observed.

Abbreviations used in this paper: AChE, acetylcholinesterase; AChR, acetylcholine receptor; -BgTx, -bungarotoxin; DIA, diaphragm; DPC, dystrophin protein complex; EDL, extensor digitorum longus; ETA, epitrochleoanconeus; NMJ, neuromuscular junction; SOL, soleus..

Please address all correspondence to K.E. Davies, Laboratory of Genetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom. Tel.: 44 1865 275324. Fax: 44 1865 275215.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Welser, J. V., Rooney, J. E., Cohen, N. C., Gurpur, P. B., Singer, C. A., Evans, R. A., Haines, B. A., Burkin, D. J. (2009). Myotendinous Junction Defects and Reduced Force Transmission in Mice that Lack {alpha}7 Integrin and Utrophin. Am. J. Pathol. 175: 1545-1554 [Abstract] [Full Text]  
• Court, F. A., Hewitt, J. E., Davies, K., Patton, B. L., Uncini, A., Wrabetz, L., Feltri, M. L. (2009). A Laminin-2, Dystroglycan, Utrophin Axis Is Required for Compartmentalization and Elongation of Myelin Segments. J. Neurosci. 29: 3908-3919 [Abstract] [Full Text]  
• Fradkin, L. G., Baines, R. A., van der Plas, M. C., Noordermeer, J. N. (2008). The Dystrophin Dp186 Isoform Regulates Neurotransmitter Release at a Central Synapse in Drosophila. J. Neurosci. 28: 5105-5114 [Abstract] [Full Text]  
• Friese, M. B., Blagden, C. S., Burden, S. J. (2007). Synaptic differentiation is defective in mice lacking acetylcholine receptor {beta}-subunit tyrosine phosphorylation. Development 134: 4167-4176 [Abstract] [Full Text]  
• O'Leary, D. A., Noakes, P. G., Lavidis, N. A., Kola, I., Hertzog, P. J., Ristevski, S. (2007). Targeting of the ETS Factor Gabp{alpha} Disrupts Neuromuscular Junction Synaptic Function. Mol. Cell. Biol. 27: 3470-3480 [Abstract] [Full Text]  
• Slater, C. R., Fawcett, P. R. W., Walls, T. J., Lyons, P. R., Bailey, S. J., Beeson, D., Young, C., Gardner-Medwin, D. (2006). Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'.. Brain 129: 2061-2076 [Abstract] [Full Text]  
• Rooney, J. E., Welser, J. V., Dechert, M. A., Flintoff-Dye, N. L., Kaufman, S. J., Burkin, D. J. (2006). Severe muscular dystrophy in mice that lack dystrophin and {alpha}7 integrin. J. Cell Sci. 119: 2185-2195 [Abstract] [Full Text]  
• Grady, R. M., Wozniak, D. F., Ohlemiller, K. K., Sanes, J. R. (2006). Cerebellar synaptic defects and abnormal motor behavior in mice lacking alpha- and beta-dystrobrevin.. J. Neurosci. 26: 2841-2851 [Abstract] [Full Text]  
• van der Plas, M. C., Pilgram, G. S. K., Plomp, J. J., de Jong, A., Fradkin, L. G., Noordermeer, J. N. (2006). Dystrophin Is Required for Appropriate Retrograde Control of Neurotransmitter Release at the Drosophila Neuromuscular Junction. J. Neurosci. 26: 333-344 [Abstract] [Full Text]  
• Janssen, P. M. L., Hiranandani, N., Mays, T. A., Rafael-Fortney, J. A. (2005). Utrophin deficiency worsens cardiac contractile dysfunction present in dystrophin-deficient mdx mice. Am. J. Physiol. Heart Circ. Physiol. 289: H2373-H2378 [Abstract] [Full Text]  
• Burkin, D. J., Wallace, G. Q., Milner, D. J., Chaney, E. J., Mulligan, J. A., Kaufman, S. J. (2005). Transgenic Expression of {alpha}7{beta}1 Integrin Maintains Muscle Integrity, Increases Regenerative Capacity, Promotes Hypertrophy, and Reduces Cardiomyopathy in Dystrophic Mice. Am. J. Pathol. 166: 253-263 [Abstract] [Full Text]  
• Krag, T. O. B., Bogdanovich, S., Jensen, C. J., Fischer, M. D., Hansen-Schwartz, J., Javazon, E. H., Flake, A. W., Edvinsson, L., Khurana, T. S. (2004). Heregulin ameliorates the dystrophic phenotype in mdx mice. Proc. Natl. Acad. Sci. USA 101: 13856-13860 [Abstract] [Full Text]  
• Shiao, T., Fond, A., Deng, B., Wehling-Henricks, M., Adams, M. E., Froehner, S. C., Tidball, J. G. (2004). Defects in neuromuscular junction structure in dystrophic muscle are corrected by expression of a NOS transgene in dystrophin-deficient muscles, but not in muscles lacking {alpha}- and {beta}1-syntrophins. Hum Mol Genet 13: 1873-1884 [Abstract] [Full Text]  
• Bassett, D. I., Currie, P. D. (2003). The zebrafish as a model for muscular dystrophy and congenital myopathy. Hum Mol Genet 12: R265-270 [Abstract] [Full Text]  
• Martin, P. T. (2003). Dystroglycan glycosylation and its role in matrix binding in skeletal muscle. Glycobiology 13: 55R-66R [Abstract] [Full Text]  
• Khanna, S., Richmonds, C. R., Kaminski, H. J., Porter, J. D. (2003). Molecular Organization of the Extraocular Muscle Neuromuscular Junction: Partial Conservation of and Divergence from the Skeletal Muscle Prototype. IOVS 44: 1918-1926 [Abstract] [Full Text]  
• Grady, R. M., Akaaboune, M., Cohen, A. L., Maimone, M. M., Lichtman, J. W., Sanes, J. R. (2003). Tyrosine-phosphorylated and nonphosphorylated isoforms of {alpha}-dystrobrevin: roles in skeletal muscle and its neuromuscular and myotendinous junctions. JCB 160: 741-752 [Abstract] [Full Text]  
• Weir, A. P., Burton, E. A., Harrod, G., Davies, K. E. (2002). A- and B-utrophin Have Different Expression Patterns and Are Differentially Up-regulated in mdx Muscle. J. Biol. Chem. 277: 45285-45290 [Abstract] [Full Text]  
• Hosaka, Y., Yokota, T., Miyagoe-Suzuki, Y., Yuasa, K., Imamura, M., Matsuda, R., Ikemoto, T., Kameya, S., Takeda, S.'i. (2002). {alpha}1-Syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration. JCB 158: 1097-1107 [Abstract] [Full Text]  
• Levi, S., Grady, R. M., Henry, M. D., Campbell, K. P., Sanes, J. R., Craig, A. M. (2002). Dystroglycan Is Selectively Associated with Inhibitory GABAergic Synapses But Is Dispensable for Their Differentiation. J. Neurosci. 22: 4274-4285 [Abstract] [Full Text]  
• Blake, D. J., Weir, A., Newey, S. E., Davies, K. E. (2002). Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle. Physiol. Rev. 82: 291-329 [Abstract] [Full Text]  
• Poon, E., Howman, E. V., Newey, S. E., Davies, K. E. (2002). Association of Syncoilin and Desmin. LINKING INTERMEDIATE FILAMENT PROTEINS TO THE DYSTROPHIN-ASSOCIATED PROTEIN COMPLEX. J. Biol. Chem. 277: 3433-3439 [Abstract] [Full Text]  
• Burkin, D. J., Wallace, G. Q., Nicol, K. J., Kaufman, D. J., Kaufman, S. J. (2001). Enhanced Expression of the {alpha}7{beta}1 Integrin Reduces Muscular Dystrophy and Restores Viability in Dystrophic Mice. JCB 152: 1207-1218 [Abstract] [Full Text]  
• Adams, M. E., Kramarcy, N., Krall, S. P., Rossi, S. G., Rotundo, R. L., Sealock, R., Froehner, S. C. (2000). Absence of {alpha}-Syntrophin Leads to Structurally Aberrant Neuromuscular Synapses Deficient in Utrophin. JCB 150: 1385-1398 [Abstract] [Full Text]  
• Rafael, J. A., Townsend, E. R., Squire, S. E., Potter, A. C., Chamberlain, J. S., Davies, K. E. (2000). Dystrophin and utrophin influence fiber type composition and post-synaptic membrane structure. Hum Mol Genet 9: 1357-1367 [Abstract] [Full Text]  
• Marques, M. J., Conchello, J.-A., Lichtman, J. W. (2000). From Plaque to Pretzel: Fold Formation and Acetylcholine Receptor Loss at the Developing Neuromuscular Junction. J. Neurosci. 20: 3663-3675 [Abstract] [Full Text]  
• Loh, N., Newey, S., Davies, K., Blake, D. (2000). Assembly of multiple dystrobrevin-containing complexes in the kidney. J. Cell Sci. 113: 2715-2724 [Abstract]  
• Amann, K. J., Guo, A. W.-X., Ervasti, J. M. (1999). Utrophin Lacks the Rod Domain Actin Binding Activity of Dystrophin. J. Biol. Chem. 274: 35375-35380 [Abstract] [Full Text]  
• Fuhrer, C., Gautam, M., Sugiyama, J. E., Hall, Z. W. (1999). Roles of Rapsyn and Agrin in Interaction of Postsynaptic Proteins with Acetylcholine Receptors. J. Neurosci. 19: 6405-6416 [Abstract] [Full Text]  
• Engel, A. G., Ohno, K., Wang, H.-L., Milone, M., Sine, S. M. (1998). REVIEW {blacksquare} : Molecular Basis of Congenital Myasthenic Syndromes: Mutations in the Acetylcholine Receptor. Neuroscientist 4: 185-194 [Abstract]  
• Moscoso, L. M., Cremer, H., Sanes, J. R. (1998). Organization and Reorganization of Neuromuscular Junctions in Mice Lacking Neural Cell Adhesion Molecule, Tenascin-C, or Fibroblast Growth Factor-5. J. Neurosci. 18: 1465-1477 [Abstract] [Full Text]  
• Nawrotzki, R, Loh, N., Ruegg, M., Davies, K., Blake, D. (1998). Characterisation of alpha-dystrobrevin in muscle. J. Cell Sci. 111: 2595-2605 [Abstract]  
• Porter, J., Rafael, J., Ragusa, R., Brueckner, J., Trickett, J., Davies, K. (1998). The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin. J. Cell Sci. 111: 1801-1811 [Abstract]  
• Newey, S. E., Howman, E. V., Ponting, Chris. P., Benson, M. A., Nawrotzki, R., Loh, N. Y., Davies, K. E., Blake, D. J. (2001). Syncoilin, a Novel Member of the Intermediate Filament Superfamily That Interacts with alpha -Dystrobrevin in Skeletal Muscle. J. Biol. Chem. 276: 6645-6655 [Abstract] [Full Text]  
• Gramolini, A. O., Belanger, G., Jasmin, B. J. (2001). Distinct regions in the 3' untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells. JCB 154: 1173-1184 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents