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Musk  -  muscle, skeletal, receptor tyrosine kinase

Rattus norvegicus

Synonyms: MuSK, Muscle, skeletal receptor tyrosine protein kinase, Muscle-specific kinase receptor, Muscle-specific tyrosine protein kinase receptor
 
 
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Disease relevance of Musk

  • Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK) [1].
 

High impact information on Musk

 

Biological context of Musk

  • Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation [4].
  • Our data extend the notion that, apart from its well documented role in AChR clustering, the MuSK complex might also be involved in the regulation of synaptic gene expression at the NMJ [5].
  • Furthermore, we found that MuSK also plays an important role in mediating hippocampal oscillatory activity in the theta frequency as well as in the induction and maintenance of long-term potentiation, two synaptic responses that correlate with memory formation [6].
 

Anatomical context of Musk

  • The receptor tyrosine kinase MuSK plays a crucial role-both as a signaling molecule and structurally-in the process of clustering nicotinic acetylcholine receptors at the neuromuscular junction [7].
  • This distribution does not result from targeting of MuSK to identified plasma membrane subdomains, and MuSK's association with itself is specific, as MuSK clusters at the cell surface are segregated from clusters of other cotransfected receptor tyrosine kinases [7].
  • Immunofluorescence microscopy of transiently transfected fibroblasts has been used to visualize the cell-surface distribution of MuSK, which is found in discrete, punctate clusters [7].
  • Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed selectively in skeletal muscle [4].
  • During neuromuscular synapse formation, agrin released from motor neurons stimulates MuSK autophosphorylation in the kinase activation loop and in the juxtamembrane region, leading to clustering of acetylcholine receptors [4].
 

Associations of Musk with chemical compounds

  • In response to doxycycline-induced agrin secretion, adult fibers did form ectopic postsynaptic specializations, even when they were electrically active, lacked fetal AChRs, and expressed normal low levels of MuSK [8].
 

Analytical, diagnostic and therapeutic context of Musk

  • Furthermore, 14-3-3 gamma was copurified by affinity chromatography with MuSK from transfected COS-7 cells and myotubes [5].
  • However, the expression of MuSK and surface AChR proteins was diminished in both myotube cultures and neuron-myotube cocultures [9].
  • Most importantly, the time-course and extent of activity-dependent gene regulation observed in primary cell culture for all genes tested, including subunits of the nicotinic acetylcholine receptor (nAChR), muscle specific kinase (MuSK), and myogenin, is reproduced in RMT lines [10].

References

  1. Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK). Jha, S., Xu, K., Maruta, T., Oshima, M., Mosier, D.R., Atassi, M.Z., Hoch, W. J. Neuroimmunol. (2006) [Pubmed]
  2. Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction. Cheusova, T., Khan, M.A., Schubert, S.W., Gavin, A.C., Buchou, T., Jacob, G., Sticht, H., Allende, J., Boldyreff, B., Brenner, H.R., Hashemolhosseini, S. Genes Dev. (2006) [Pubmed]
  3. MAGI-1c: a synaptic MAGUK interacting with muSK at the vertebrate neuromuscular junction. Strochlic, L., Cartaud, A., Labas, V., Hoch, W., Rossier, J., Cartaud, J. J. Cell Biol. (2001) [Pubmed]
  4. Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation. Till, J.H., Becerra, M., Watty, A., Lu, Y., Ma, Y., Neubert, T.A., Burden, S.J., Hubbard, S.R. Structure (Camb.) (2002) [Pubmed]
  5. 14-3-3 gamma associates with muscle specific kinase and regulates synaptic gene transcription at vertebrate neuromuscular synapse. Strochlic, L., Cartaud, A., Mejat, A., Grailhe, R., Schaeffer, L., Changeux, J.P., Cartaud, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. MuSK expressed in the brain mediates cholinergic responses, synaptic plasticity, and memory formation. Garcia-Osta, A., Tsokas, P., Pollonini, G., Landau, E.M., Blitzer, R., Alberini, C.M. J. Neurosci. (2006) [Pubmed]
  7. Cell-surface MuSK self-association: a crucial role for the putative signal sequence. Bianchetta, M.J., Betensky, R.A., Cohen, J.B. Biochemistry (2005) [Pubmed]
  8. Electrical activity and postsynapse formation in adult muscle: gamma-AChRs are not required. Hashemolhosseini, S., Moore, C., Landmann, L., Sander, A., Schwarz, H., Witzemann, V., Sakmann, B., Brenner, H.R. Mol. Cell. Neurosci. (2000) [Pubmed]
  9. Thrombin reduces MuSK and acetylcholine receptor expression along with neuromuscular contact size in vitro. Faraut, B., Ravel-Chapuis, A., Bonavaud, S., Jandrot-Perrus, M., Verdière-Sahuqué, M., Schaeffer, L., Koenig, J., Hantaï, D. Eur. J. Neurosci. (2004) [Pubmed]
  10. Activity-dependent gene regulation in conditionally-immortalized muscle precursor cell lines. Macpherson, P.C., Suhr, S.T., Goldman, D. J. Cell. Biochem. (2004) [Pubmed]
 
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