Abstract
The neuromuscular junction (NMJ) is a tripartite synapse in which not only presynaptic and post-synaptic cells participate in synaptic transmission, but also terminal Schwann cells (TSC). Acetylcholine (ACh) is the neurotransmitter that mediates the signal between the motor neuron and the muscle but also between the motor neuron and TSC. ACh action is terminated by acetylcholinesterase (AChE), anchored by collagen Q (ColQ) in the basal lamina of NMJs. AChE is also anchored by a proline-rich membrane anchor (PRiMA) to the surface of the nerve terminal. Butyrylcholinesterase (BChE), a second cholinesterase, is abundant on TSC and anchored by PRiMA to its plasma membrane. Genetic studies in mice have revealed different regulations of synaptic transmission that depend on ACh spillover. One of the strongest is a depression of ACh release that depends on the activation of α7 nicotinic acetylcholine receptors (nAChR). Partial AChE deficiency has been described in many pathologies or during treatment with cholinesterase inhibitors. In addition to changing the activation of muscle nAChR, AChE deficiency results in an ACh spillover that changes TSC signaling. In this mini-review, we will first briefly outline the organization of the NMJ. This will be followed by a look at the role of TSC in synaptic transmission. Finally, we will review the pathological conditions where there is evidence of decreased AChE activity.
Highlights
Specialty section: This article was submitted to Brain Disease Mechanisms, a section of the journal Frontiers in Molecular Neuroscience
One of the strongest is a depression of ACh release that depends on the activation of α7 nicotinic acetylcholine receptors
Synaptic transmission results in several sequential steps: (1) depolarization of the motor neuron membrane triggers the simultaneous release of dozens of vesicles filled with acetylcholine (Ach) and ATP; (2) synchronous activation of nicotinic acetylcholine receptors clustered on the crest of the post-synaptic membrane that depolarizes the membrane and triggers an action potential; (3) termination of the action of ACh by hydrolysis with acetylcholinesterase (AChE) localized in the synaptic cleft and anchored in basal lamina via a collagen-like tail [collagen Q (ColQ)]
Summary
Specialty section: This article was submitted to Brain Disease Mechanisms, a section of the journal Frontiers in Molecular Neuroscience. In addition to changing the activation of muscle nAChR, AChE deficiency results in an ACh spillover that changes TSC signaling In this mini-review, we will first briefly outline the organization of the NMJ. Butyrylcholinesterase (BChE) is detectable at the NMJ (Davis and Koelle, 1967), BChE is anchored by PRiMA at the surface of TSC (Petrov et al, 2014) These enzymes (AChE and BChE), localized and clustered in different compartments of the NMJ, efficiently eliminate ACh and prevent ACh spillover and limit the action of ACh to a single shot to the post-synaptic receptors
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