Pathways & interactions
Nicotinic acetylcholine receptor (IPR002394)
Short name: Nicotinic_acetylcholine_rcpt
Overlapping homologous superfamilies
- Neurotransmitter-gated ion-channel (IPR006201)
- Nicotinic acetylcholine receptor (IPR002394)
Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses [PMID: 1721053, PMID: 1846404]. Five of these ion channel receptor families have been shown to form a sequence-related superfamily:
- Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits [PMID: 18446614].
- Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits [PMID: 15383648].
- Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known [PMID: 18760291].
- Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) [PMID: 10026168].
- Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) [PMID: 15165736].
These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence [PMID: 1721053, PMID: 1846404].
Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate signal transduction at the post-synaptic membrane of cholinergic synapses, such as the neuromuscular junction [PMID: 1721053]. They belong to a family of neurotransmitter-gated receptors, including glycine, gamma-aminobutyric-acid (GABA), serotonin 5HT3 receptors. These are oligomeric transmembrane (TM) complexes (pentamers of 2 alpha and 1 beta, 1 gamma and 1 delta subunit) that contain a central channel, which transiently opens upon binding of a specific neurotransmitters. Their sequences are related and share the same topology: each has an extracellular, glycosylated N-terminal ligand-binding domain; 3 hydrophobic TM regions, which form the channel; a hydrophilic cytoplasmic domain; followed by a fourth putative TM region [PMID: 2465296]. The nicotinic receptor ligand binding domain is a specialised pocket of aromatic and hydrophobic residues formed at interfaces between protein subunits that changes conformation to convert agonist binding into gating of an intrinsic ion channel [PMID: 12436411].
The expression of acetylcholine receptors is activated during muscle differentiation and upon denervation of adult muscle [PMID: 2311580]. Receptor function is regulated by phosphorylation and dephosphorylation by kinases and phosphatases present in the post-synaptic membranes [PMID: 1721053]. Most of the phosphorylation sites are located in the major intracellular loop between the third and fourth TM regions and are closely spaced.
- PR00254 (NICOTINICR)