It is a receptor tyrosine kinase required for the formation of musk (muscle-specific kinase) neuromuscular junction. The activated by nerve derived proteoglycan called agrin.
It is called agrin development of growth at the end of the axon of the motor neuron protein secretion. This protein binds to several receptors on the surface of skeletal muscle. Receptor appears to be required to form neuromuscular junctions comprising synapses, called (muscle specific kinase) musk (NMJ). Phosphate molecule, it means that cause the addition of proteins that bind to the cytoplasmic domain of a receptor and tyrosine itself specific to induce cell signaling – a musk receptor tyrosine kinases. Requirements for the formation of the NMJ musk, studies have shown mice (“knockout”) mainly. In mice lacking the musk or agrin, neuromuscular junction is not formed. Proteins also many other, it is necessary to maintain the integrity and comprises NMJ. For example, also musk, I bind to a protein called “down-to-tyrosine kinase 7” and (Dokdo 7). The DOK-7, or stabilize the musk, PTB domain binding the musk that is phosphorylated working actively to increase the kinase activity of musk.
When activated by its ligand agrin, in order to induce acetylcholine receptor ‘clusters’ of (ACHR), musk signals by protein called rapsyn (CK2), and islets seven casein kinase 2. Inhibition of CK2 mice lacking 7 ACHR Dokdo, and, as failed to form the neuromuscular synapse or cluster, so interfere with the recruitment of ACHR to primary musk, both of Dokdo 7 and CK2 , scaffolding is required for the formation of musk induced neuromuscular junction. In addition to the protein, then, other proteins are assembled to form a plate of the neuromuscular junction. Plate of the neuromuscular junction, forming ends nerve – structure required for the transmission of nerve impulses in the muscle is used to detect muscle contraction.
Antibodies for this protein has been found in patients with myasthenia gravis showing no antibody at all acetylcholine receptor (negative). It is believed that the disease will lead to the acetylcholine receptor of autoimmune activity loss still, but the phenotype of these patients, it appears to be different from the myasthenia of patients with many other more likely than women , possibility throat and neck, and African-American ethnicity in the likelihood of eye part has a weakness is high is high.
Comparison of discrimination nerve endings, and as a result, neuromuscular junction, receive depends on the interaction of mutual induction between the muscle and nerve development patches highly specialized membrane of muscle called the motor plate. Agrin is a nerve-derived factor that can cause a molecular rearrangement of the motor plate, but it remains poorly understood mechanism of action of agrin. Musk is likely to be disposed key nerve signals to be received even localized receptor tyrosine kinase plates engine. The generated Recently, mice deficient in musk and agrin, have shown a profound defect also in the neuromuscular junction thereof. Here, agrin has been demonstrated to act via a receptor complex comprising a subcomponent myotube-specific and musk.
Culminating in exact juxtaposition of nerve highly specialized ending with complex molecular structure of the postsynaptic surface of the muscle, motor axons grow, the formation of neuromuscular synapses, induction effect between the differentiation of muscle cells I need a set of. Signaling pathways and receptors are not best known to mediate the interaction of these induced. We targeted disruption of the gene encoding the musk, was produced in the mouse localized receptor tyrosine kinases in the postsynaptic muscle surface selectively. Suggesting the lack of inducing the formation of synaptic neuromuscular junction, and is not formed in these mice. The results of the accompanying document, our results have shown that it meets the critical nerves received (agrin) signal musk, synapses containing tissue postsynaptic membrane of synaptic specific transcription sequentially with The synaptic activation and differentiation signaling cascades responsible for all aspects of the formation.
We created a yeast two-hybrid bait representing the native intracellular domain of musk active. For this purpose, condensing the full intracellular domain of two flexible included musk we. To determine connection musk actor potential whether dependent phosphorylation state of musk, we generated a structure similar to inactive kinase domain. Bait constructs both, is expressed in COS7 cells and its yeast. In MuSK2xkd not autophosphorylation, it was observed in MuSK2xwt. We checked the independent colonies of about 6 × 106 of yeast and yeast two-hybrid analysis using the MuSK2xwt as bait. One of the candidates, the identification of the CK2 β subunit many times independently we. By coimmunoprecipitations things in HEK293 cells transiently transfected, we have confirmed this interaction. Incidentally, HEK293 cells should be noted that it contains endogenous CK2 further. In CK2β subunit and reacted with tyrosine phosphorylated form of the intracellular domain of musk represented by the slower migrating band of the two bands of the size of MuSK2xwt and preferably. We will extend the study of the interaction of CK2 with the α subunit by CK2 acts as a tetramer holoenzim mainly. Both subunits, which interact with the intracellular domain of musk, but the interaction with the α subunit is very weak. I’ll make sure the interaction of musk and CK2α CK2β or whether carried out in the presence of both CK2 subunits then.
That means connecting the musk epitope CK2α they do not overlap, and CK2β,. I is precipitated in the presence of CK2α precipitation result of tyrosine phosphorylated form of MuSK2xwt primarily CK2βMuSK2xwt. In addition, I can if precipitation MuSK2xwt of cells co-expressing the CK2 subunit of both, we CK2α co-precipitation. These experiments, shows the interaction of the catalytic subunit and between CK2 regulation of co-expression of CK2 subunits of other regardless of the musk. Interaction of CK2β subunit between CK2α asked to see if you are affected by the presence of musk then. In spite of the presence of musk, we observed a co-precipitation of CK2α by CK2β. Finally, evidenced by co-immunoprecipitation of endogenous protein of myotubes treated with agrin synaptic area and control neurons and muscle, such as musk, I reacted with CK2β under physiological conditions. In recent years, several publications are, explain the CK1 protein as an important mediator of the Wnt pathway. To test the binding potential members of the Wnt pathway, is CK2βWnt signaling, we examined musk CK1 or receptor protein whether bind specifically to interact with each other. The specific expression of the lack of interaction with the exception of the interaction between the musk Wnt receptor in myotubes and C2C12 myoblasts, and CK2β and CK1 protein substantially all.