Structure and function of neuromuscular junction, centered on muscle-specific tyrosine kinase and related proteins
| Autor: | Masaharu Takamori |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
animal structures Agrin biology Chemistry Immunology Neuroscience (miscellaneous) Wnt signaling pathway Anatomy Neuromuscular junction Receptor tyrosine kinase Cell biology Dystroglycans 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immunology and Microbiology (miscellaneous) Postsynaptic potential medicine biology.protein Neurology (clinical) Tyrosine kinase 030217 neurology & neurosurgery Acetylcholine receptor |
| Zdroj: | Clinical and Experimental Neuroimmunology. 7:215-225 |
| ISSN: | 1759-1961 |
| Popis: | Muscle-specific tyrosine kinase (MuSK) is uniquely positioned as a key protein in the neuromuscular junction, particularly in relation to acetylcholine receptor (AChR) clustering in the postsynaptic membrane, and pre- and postsynaptic differentiations. The present review focuses on the functional mechanisms in the neuromuscular junction structures centered on MuSK and related proteins. (i) The Wnt non-canonical pathway through the Wnt/MuSK cysteine-rich domain (coreceptor: low-density lipoprotein receptor-related protein 4 [Lrp4])/Dishevelled (scaffolding protein) signaling; this localizes aneural microclusters of AChR at the central part of the postsynaptic membrane in parallel with axonal guidance, and converges on the neural agrin/Lrp4/MuSK immunoglobulin-like domains 1 and 2 (Ig 1/2 domains) pathway to form innervated full-sized AChR clusters. (ii) The presynaptic homeostasis (upregulation of acetylcholine release) compensates postsynaptic impairments by the fast-mode of endocytosis in the nerve terminal and the trans-synaptic retrograde signals including Wnt-MuSK cysteine-rich domain canonical pathway (including β-catenin), Lrp4 and laminin β2. (iii) The extracellular matrix contributive to the neuromuscular junction formation and maintenance includes collagen Q, perlecan, biglycan and dystroglycans; collagen Q and biglycan link to MuSK (first and second immunoglobulin-like domains and cysteine-rich domain) and acetylcholinesterase on one hand and to the intracellular cytoskeleton through dystroglycans on the other hand, so that MuSK participates in not only AChR clustering at the muscle surface and acetylcholinesterase-controlled muscle membrane sensitivity to acetylcholine, but also the postsynaptic stability reinforced by cytoskeletal dynamics; the laminin network including muscle agrin also contributes to synaptic stability through dystroglycans; the agrin-enhanced phosphorylation of cortactin promotes cytoskeletal dynamics to stabilize AChR clusters; the interaction of neuregulin 1 with the receptor tyrosine kinase of EGF receptor family (ErbB receptor) contributes to the postsynaptic stabilization and also MuSK phosphorylation leading to AChR clustering. (iv) The muscle contractile mechanisms are controlled by release and restoration of the sarcoplasmic Ca2+ being mediated through the receptor and channel proteins. Insight into these fine structures will foster further immunological approaches to search for new antigenic targets and to enhance antibody detection in myasthenia gravis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|