MUSK Membrane Protein Introduction

Introduction of MUSK

MUSK is a transsynaptic membrane protein specifically expressed in neuromuscular junctions, with a molecular weight of 100 kDa, colocalized with AChR. As an ideal candidate antigen for anti-AChR-negative MG, MUSK plays a very important role in the development and maintenance of neuromuscular junctions. In the postsynaptic membrane, MUSK is associated with low-density lipoprotein receptor-associated protein 4 (Lrp4). Binding of neurosecretion agrin to Lrp4 activates MUSK through phosphorylation, and phosphorylated MUSK triggers complex intracellular signaling pathways, recruits and activates non-receptor tyrosine kinases and GTPases through Dok-7, resulting in AChR assembly.

Function of MUSK Membrane Protein

MUSK is located at the posterior junction of the neuromuscular junction. It is involved in agrin signaling, allowing AChRs to accumulate at the neuromuscular junction. MUSK activation in skeletal muscle is primarily responsible for the accumulation of AChR at the neuromuscular junction. The binding of MUSK pY553 to the phosphotyrosine domain of the adaptor protein DOK7 is involved in the activation of MUSK, and the agrin released at the axon end binds to LRP4 in muscle to activate MUSK, forming a polyprotein-LRP4 tetramer complex, which further stimulates MUSK dimerization and transphosphorylation of three tyrosine residues in the activation loop of MUSK, increasing its catalytic activity. The activated musk interacts with rapsyn, a scaffold protein, which causes the acetylcholine receptor to aggregate at the neuromuscular junction.

Fig.1 In the postsynaptic membrane, muscle-specific tyrosine kinase (MuSK) is related to low-density lipoprotein receptor-associated protein 4 (Lrp4). MuSK activation by agrin-Lrp4 binding triggers a signaling pathway that includes Dok7 recruitment, resulting in AChR clustering. Acetylcholinesterase (AChE) binds to perlecan and MuSK via its collagen Q (ColQ) tail. (Evoli, 2011)

Application of MUSK Membrane Protein in Literature

1. Rivner M.H., et al. Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies. Neurologic Clinics. 2018, 36(2): 293-310. PubMed ID: 29655451
   
   

   This article finds that Muscle-specific tyrosine kinase antibody (MuSK), which accounts for 30% to 40% of the cause of myasthenia gravis, is associated with a specific clinical phenotype of anti-MuSK myasthenia gravis.

2. Koneczny I., et al. The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. Journal of Anatomy. 2013, 224(1): 29-35. PubMed ID: 23458718
   
   

   This review describes the clinical aspects of distinguishing MuSK MG from AChR MG and the role of MuSK in the development and function of neuromuscular junctions and discusses the failure of data to address how MuSK antibodies cause neuromuscular conduction.

3. Takamori M., et al. Antibodies against Wnt receptor of muscle-specific tyrosine kinase in myasthenia gravis. Journal of Neuroimmunology. 2013, 254(1-2): 183-6. PubMed ID: 22999188
   
   

   This article suggests that the binding of the MuSK antibody to the functional domain of MuSK is heterogeneous.

4. Lee J.Y., et al. Transient neonatal myasthenia gravis due to a mother with ocular onset of anti-muscle specific kinase myasthenia gravis. Neuromuscular Disorders. 2017, 27(7): 655-657. PubMed ID: 28495046
   
   

   This article speculates that neonates have anti-MuSK-mediated transient myasthenia gravis, so MuSK antibody testing is necessary for pregnant women who may be myasthenia gravis to inform transient neonatal myasthenia gravis.

5. Kirzinger L., et al. Myopathy in Childhood Muscle-Specific Kinase Myasthenia Gravis. Pediatric Neurology. 2016, 65: 90-92. PubMed ID: 27697312
   
   

   This article first lists examples of myasthenia gravis syndrome and studies the hypothesis that mitochondrial myopathy is a pathogenic mechanism of MuSK antibody-positive myasthenia gravis.

MUSK Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-MUSK antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Evoli A and Lindstrom J. (2011). Myasthenia gravis with antibodies to MuSK: another step toward solving the mystery? Neurology. 77(20): 1783-4.

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