[Cholinesterases: anchored enzymes in membranes and basal laminae].
Two proteins, ColQ and PRiMA, organize tetramers of acetylcholinesterase (AChE) and of butyrylcholinesterase (BChE) through peptide interactions. A short proline rich sequence in the N-terminal domain of ColQ or PRiMA associates four C-terminal extension of AChE or BChE. ColQ targets the enzymes in the basal lamina, PRiMA targets the enzymes at the plasma membrane. These complexes represent the mature proteins. The unassembled C-terminal extention of AChE is the key determinant recognized during the "quality control" of protein synthesis. Unassembled catalytic subunits are then degraded by the proteasome pathway. At the neuromuscular junction, ColQ/AChE represents the concentrated enzyme. The clusterisation of AChE depends upon ColQ through three sites of interactions: two different heparin binding domains in the collagen domain interact with heparan sulfate proteoglycan particularly the perlecan and the C-terminal non collagenic domain interacts with MuSK, the tyrosine kinase receptor organiser of the neuromuscular junction. The absence of ColQ and AChE has revealed that the excess of Ach stimulates more nicotinic receptors but probably not until their desensitization. Several morphological modifications may help the clearance of Ach. Conversely the synapse transmission fails during high frequency nerve stimulation.
Krejci
Eric
E
Laboratoire de Neurologie Moléculaire et Cellulaire, CNRS-ENS UMR 8544, 75005 Paris. eric.krejci@univ-paris5.fr
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D001485:Basement Membrane / Q000201:enzymology*; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology*; D002802:Cholinesterases / Q000737:chemistry / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D009124:Muscle Proteins / Q000737:chemistry / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D013569:Synapses / Q000502:physiology
D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C446290:PRIMA1 protein, human; D003094:Collagen; D000110:Acetylcholinesterase; C114027:COLQ protein, human; D002091:Butyrylcholinesterase; D002802:Cholinesterases