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Essay Topic 5. Neuromuscular Junction As Site Of Disease Process. And Formation Of Nuromuscular Junction.

3184 words - 13 pages

Essay topic 5.5. The neuromuscular junction as a site of disease processProteins involved in formation of the neuromuscular junctionThe neuromuscular junction is a specialized junction, where a motor nerve forms its synaptic terminal with a muscle fibre, one of many fibres that make up a whole muscle. The mature neuromuscular junction is composed of three types of cells - a motor nerve terminal, a muscle fibre and a Schwann cell covering the junction. All three of these cells are highly differentiated and specialized for their functions (Kandel 2000, p. 1089).The events that occur during the formation of the neuromuscular junction have been extensively studied and are the most comprehensively understood of any nerve-to-target cell contact.Prior to formation of the synapse all three components of the neuromuscular junction develop and acquire identities independently. The muscle cells are derived from the mesoderm and migrate from the dermomyotomal portion of the somite. Motoneurons migrate from the ventricular zone of the neural tube to a ventral-lateral location before axons grow out of the spinal cord. Schwann cells are glial cells, which insulate the axons outside of the spinal cord, they are derived from neural crest cells and associate with axons from the somite onwards to the peripheral target.At the time of the first axons reaching the developing muscle, the muscle fibres are myoblasts that have just fused to form multinucleated myotubes, there is no evidence to suggest that motor neurons prefer certain site on the developing myotube or that there is a predetermined site for the formation of the synapse, on the contrary, synapse formation can occur on most, if not all of the myotube surface (Lichtman et al in Zigmond et al 2000, pp. 547-8). Acetylcholine receptors (AChR) are found uniformly dispersed over the surface of the myotube until the nerve approaches the myotube. As the nerve approaches the myotube a protein known as agrin, which is synthesized in the motor neuron, is transported down the axon to the synaptic cleft where it is released from the nerve terminal, here it is deposited in the synaptic basal lamina. The major components of the basal lamina are laminins, which are made up of α, β and γ chains; it forms a continuous non-myelin layer over the nerve terminal and is a potent promoter of axon outgrowth. The basal lamina is present (at least components of the basal lamina are present) prior to the arrival of the nerve and is rich in the enzyme acetylcholinesterase (AChE), an enzyme which catalyses the breakdown of acetylcholine (ACh) the major neurotransmitter at the neuromuscular junction.Agrin acts through receptors in the plasma membrane of the muscle fibre, it brings about the localization of the AChR to the region below the nerve terminal, the aggregation of AChR is essential for the development of the neuromuscular junction. Agrin also regulates the distribution of other synaptic proteins, such as AChE,...

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