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muscarinic M1 receptor; muscarinic acetylcholine receptor M1 (CHRM1)
Function:
- role in breakdown of phosphoinositides & modulation of K+ channels through the action of G proteins
- the muscarinic M1 receptor is a post-synaptic receptor that appears to induce a facilitory response in post-synaptic neurons, perhaps contributing to learning & memory through facilitation of synaptic remodeling [3]
- as with other muscarinic receptors, the M1 receptor is a serpentine receptor transducing the binding of its ligand via intracellular G proteins
- it is linked to phosphatidylinositol (PI) turnover.
- interacts with GPRASP2
Structure: belongs to the G-protein coupled receptor 1 family
Compartment:
- cell membrane, cell junction, synapse
- postsynaptic cell membrane
Expression:
- the muscarinic M1 receptor is the most abundant muscarinic receptor in the cerebral cortex
- also found in the dentate gyrus, hippocampus, anterior olfactory nucleus, olfactory tubercle & nucleus accumbens.
Pathology:
- stimulation of the M1 receptor may diminish phosphorylation of microtubule associated protein tau, an initial step in the formation of paired helical filaments & neurofibrillary tangles associated with Alzheimer's disease [2]
- blockade of the M1 receptor causes typical anticholinergic effects:
1) constipation
2) blurred vision
3) dry mouth
4) drowsiness
Interactions
molecular events
General
muscarinic receptor
phosphoprotein
Properties
SIZE: entity length = 460 aa
MW = 51 kD
COMPARTMENT: synaptic membrane
CELL: neuron
MOTIF: exoplasmic domain {1-24}
MOTIF: N-glycosylation site {N2}
N-glycosylation site {N12}
transmembrane domain {25-47}
cytoplasmic domain {48-61}
transmembrane domain {62-82}
exoplasmic domain {83-99}
MOTIF: cysteine residue {C98}
MODIFICATION: cysteine residue {C178}
transmembrane domain {100-121}
cytoplasmic domain {122-141}
transmembrane domain {142-164}
exoplasmic domain {165-186}
MOTIF: cysteine residue {C178}
MODIFICATION: cysteine residue {C98}
transmembrane domain {187-209}
cytoplasmic domain {210-366}
transmembrane domain {367-387}
exoplasmic domain {388-401}
transmembrane domain {402-421}
cytoplasmic domain {422-460}
MOTIF: Thr phosphorylation site {T428}
Ser phosphorylation site {S451}
Thr phosphorylation site {T455}
Ser phosphorylation site {S457}
MISC-INFO: pKi [PIRENZEPINE] 8.0
pKi [TELENZEPINE] 9.1
pKi [MT_7_TOXIN] 9.8
Database Correlations
OMIM 118510
UniProt P11229
Pfam PF00001
Entrez Gene 1128
Kegg hsa:1128
References
- Conkilin et al PNAS 85:8698 (1988)
- Mesulam M.
The cholinergic lesion of Alzheimer's disease: pivotal factor
or side show?
Learn Mem. 2004 Jan-Feb;11(1):43-9. Review.
PMID: 14747516
- Greenfield's Neuropathology, 5th ed., 1992 p.1328
- UniProt :accession P11229