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

• The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction [2].
• Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction [2].
• We observed CK2-mediated phosphorylation of serine residues within the kinase insert (KI) of MuSK [2].
• In an attempt to identify partners and/or effectors of MuSK, cross-linking and immunopurification experiments were performed in purified postsynaptic membranes from the Torpedo electrocyte, a model system for the NMJ [3].
• A bona fide MAGI-1c (150 kD) was detected by Western blotting in the postsynaptic membrane of Torpedo electrocytes, and in a high molecular mass cross-link product of MuSK [3].

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