Cholinesterases in Tripartite Neuromuscular Synapse

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.

A method to investigate muscle target‐specific transcriptional signatures of single motor neurons

“…However, cells of the left‐most cluster showed a higher transcript count for TUBB3 , and an overall higher number of genes detected than for the other cluster (greyscale, above). Interestingly, the majority of cells (21 out of the 24) presenting a good cDNA profile, expressed Choline Acetyltransferase ( CHAT ), Acetylcholinesterase subunit Q ( COLQ ), and Vesicular Acetylcholine Transporter ( SLC18A3 ), three gene members of the biosynthesis and transport chain of the motor neuron‐specific neurotransmitter acetylcholine 29 . CPLX1 and SCNA , both known to be involved in the modulation of neurotransmitter action and implicated in motor neuron diseases were also expressed by these cells 30,31 .…”

“…Interestingly, the majority of cells (21 out of the 24) presenting a good cDNA profile, expressed Choline Acetyltransferase ( CHAT ), Acetylcholinesterase subunit Q ( COLQ ), and Vesicular Acetylcholine Transporter ( SLC18A3 ), three gene members of the biosynthesis and transport chain of the motor neuron‐specific neurotransmitter acetylcholine. 29 CPLX1 and SCNA , both known to be involved in the modulation of neurotransmitter action and implicated in motor neuron diseases were also expressed by these cells. 30 , 31 Furthermore, the cells also expressed FOXP1 and ALDH1A2 , two well‐known embryonic marker genes of developing LMC motor neurons (left most cluster in Figure 4D ).…”

Bringing synapses into focus: Recent advances in synaptic imaging and mass-spectrometry for studying synaptopathy

“…Despite synaptosomes being widely used as an ex vivo model, there is increasing evidence to support the idea that synapses consist of more than just pre- and postsynaptic terminus ( Chung and Barres, 2012 ; Henstridge et al, 2019 ; Morizawa et al, 2022 ). The tripartite synapse acknowledges the important role that glial cells play in synaptic function: astrocytes, microglia, and oligodendrocytes support synapses within the central nervous system (CNS), and Schwann cells support the neuromuscular junction (NMJ) in the peripheral nervous system ( Perea et al, 2009 ; Petrov et al, 2021 ). Glia have roles crucial for proper synaptic function, including clearance and reuptake of neurotransmitters, Ca 2+ homeostasis, receptor distribution, phagocytosing synaptic material, and synaptogenesis ( Murphy-Royal et al, 2017 ; Um, 2017 ; Kono et al, 2021 ; Shan et al, 2021 ; di Benedetto et al, 2022 ).…”

The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution

“…But in-depth investigation and research of BuChE, a more important function of BuChE have been proposed, including memory, selective attention, and behavioral response (13,14). Petrov et al (15) and others found that BuChE can be expressed in specific brain areas, such as the amygdala, hippocampus, and frontal lobe, seems to be involved in the development of certain aspects of the nervous system, and expresses nicotinic acetylcholine (ACh) receptors. This suggests that BuChE may regulate the functional state of cells by hydrolyzing the neurotransmitter ACh.…”