Acetylcholine receptors clusters

R. J. Bloch, M. Velez, J. Krikorian, and D. Axelrod, Microfilaments and actin-associated proteins at sites of membrane-substrate attachment within acetylcholine receptor clusters, Exp. Cell Res. 182, 583-596 (1989). 

Braithwaite, A.W., Harris, A.J. (1979). Neural influence on acetylcholine receptor clusters during embryonic development of skeletal muscles. Nature (Land.) 279 549-51. 

Stetzkowski-Marden F, Gaus K, Recouvreur M, Cartaud A, Cartaud J (2006) Agrin elicits membrane lipid condensation at sites of acetylcholine receptor clusters in C2C12 myotubes. J Lipid Res 47 2121-2133... 

Tourovskaia, A., Kosar, T. F., and Folch, A., Local induction of acetylcholine receptor clustering in myotube cultures using microfluidic apphcation of agrin, Biophys J, 90, 2192, 2006. 

Once the neurotransmitter is released from the presynaptic terminal it diffuses across the synaptic cleft. On the postsynaptic side it complexes with a membrane-bound macromolecule, its receptor. In synapses that have to generate action potentials within microseconds of neurotransmitter release, the receptors must be clustered in the postsynaptic membrane at high density, close to where the neurotransmitter is released. Such a synapse exists at the neuromuscular junction, where acetylcholine is the neurotransmitter. Acetylcholine is released from the presynaptic nerve terminal within 50 nm of the postsynaptic muscle membrane that contains densely arrayed acetylcholine receptors ( 10,000 acetylcholine rcccptors/pm2). There is a steady turnover of receptors, with newly synthesized receptors replacing those that are periodically degraded or not being utilized. 

TTP also appears to have regulatory properties on proteins involved in the clustering of acetylcholine receptors (Gautam et al., 1995). 

Bloch RJ, Bezakova G, Ursitti JA, Zhou D, Pumplin DW (1997) A membrane skeleton that clusters nicotinic acetylcholine receptors in muscle. Soc Gen Physiol Ser 52 177-195. 

Clustering of novel with known genes [8]. The ESTs (expressed sequence tags), SC6 and SC7 cluster with neurotransmitter-related genes. Upper right panel SC6 has a temporal expression pattern similar to that of nAChRd (nicotinic acetylcholine receptor delta subunit). Lower left panel ... 

By the time of innervation at G16, the acetylcholine receptors (AChRs) which had been scattered along the length of the immature muscle fibers, cluster at the areas which will become the neuromuscular junction (Anderson and Cohen, 1977), a phenomenon that is at least partially dependent upon the release of agrin from the approaching axon terminal (McMahan et al., 1980). 

The basal lamina hypothesis infers that there is a fixed synaptic site that attracts regenerating axons. However, synaptic sites are not fixed, but can be induced anywhere along the length of a dener-vated muscle fiber by contact with axons (Elsberg, 1917 Fex et al., 1966 Frank et al., 1974). Agrin released from axons may aid in this process by inducing the clustering of acetylcholine receptors. 

Fig. 6.3 Adult neuromuscular junction with the three cells that constitute the synapse the motor neuron (i.e. nerve terminal), muscle fibre and Schwann cell. The motor neuron from the ventral horn of the spinal cord innervates the muscle. Each fibre receives only one synapse. The motor nerve loses its myelin to terminate on the muscle fibre. The nerve terminal, covered by Schwann cell, has vesicles clustered about the membrane thickenings, which are the active zones, towards its synaptic side and mitochondria and microtubules towards its other side. A synaptic gutter, made up of primary and many secondary clefts, separates the nerve from the muscle. The muscle surface is cormgated, and dense areas on the shoulders of each fold contain acetylcholine receptors. The sodium channels are present at the clefts and throughout the musele membrane (from Martyn 2005, p 863 copyright Elsevier)...

Vesicle You should demonstrate that there are two stores of acetylcholine (ACh), one deep in the nerve terminal and one clustered beneath the surface opposite the ACh receptors in the so-called active zones . The deep stores serve as a reserve of ACh while those in the active zones are required for immediate release of ACh into the synaptic cleft. 

The desensitization of most GPCRs appears to be dependent on the carboxyl tail or third intracellular loop regions. For example, the cx -adrenergic (132), the a,g-adrenergic (133), the N-formyl peptide (134), and the M2 muscarinic acetylcholine (135,136) receptors aU contain clusters of residues in the third intracellular loop that are required for desensitization. 

ACETYLCHOLINE In most regions of the CNS, the effects of ACh, assessed either by iontophoresis or by radioligand-binding assays, appear to be generated by interaction with a mixture of nicotinic and muscarinic receptors. Several presumptive chohnergic pathways have been proposed in addition to that of the motoneuron-Renshaw cell. Eight major clusters of ACh neurons and their pathways have been characterized. 

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