Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM
Rapid communication at the chemical synapse depends on the action of ion channels residing in the postsynaptic membrane. The channels open transiently upon the binding of a neurotransmitter released from the presynaptic nerve terminal, eliciting an electrical response. Membrane lipids also play a vi...
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| Format: | Article |
| Language: | English |
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International Union of Crystallography
2017-07-01
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| Series: | IUCrJ |
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| Online Access: | http://scripts.iucr.org/cgi-bin/paper?S2052252517005243 |
| _version_ | 1828143202421440512 |
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| author | Nigel Unwin |
| author_facet | Nigel Unwin |
| author_sort | Nigel Unwin |
| collection | DOAJ |
| description | Rapid communication at the chemical synapse depends on the action of ion channels residing in the postsynaptic membrane. The channels open transiently upon the binding of a neurotransmitter released from the presynaptic nerve terminal, eliciting an electrical response. Membrane lipids also play a vital but poorly understood role in this process of synaptic transmission. The present study examines the lipid distribution around nicotinic acetylcholine (ACh) receptors in tubular vesicles made from postsynaptic membranes of the Torpedo ray, taking advantage of the recent advances in cryo-EM. A segregated distribution of lipid molecules is found in the outer leaflet of the bilayer. Apparent cholesterol-rich patches are located in specific annular regions next to the transmembrane helices and also in a more extended `microdomain' between the apposed δ subunits of neighbouring receptors. The particular lipid distribution can be interpreted straightforwardly in relation to the gating movements revealed by an earlier time-resolved cryo-EM study, in which the membranes were exposed briefly to ACh. The results suggest that in addition to stabilizing the protein, cholesterol may play a mechanical role by conferring local rigidity to the membrane so that there is productive coupling between the extracellular and membrane domains, leading to opening of the channel. |
| first_indexed | 2024-04-11T19:53:12Z |
| format | Article |
| id | doaj.art-02437f89e5f94a81a0d1dee32a491145 |
| institution | Directory Open Access Journal |
| issn | 2052-2525 |
| language | English |
| last_indexed | 2024-04-11T19:53:12Z |
| publishDate | 2017-07-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | IUCrJ |
| spelling | doaj.art-02437f89e5f94a81a0d1dee32a4911452022-12-22T04:06:14ZengInternational Union of CrystallographyIUCrJ2052-25252017-07-014439339910.1107/S2052252517005243hi5645Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EMNigel Unwin0MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, EnglandRapid communication at the chemical synapse depends on the action of ion channels residing in the postsynaptic membrane. The channels open transiently upon the binding of a neurotransmitter released from the presynaptic nerve terminal, eliciting an electrical response. Membrane lipids also play a vital but poorly understood role in this process of synaptic transmission. The present study examines the lipid distribution around nicotinic acetylcholine (ACh) receptors in tubular vesicles made from postsynaptic membranes of the Torpedo ray, taking advantage of the recent advances in cryo-EM. A segregated distribution of lipid molecules is found in the outer leaflet of the bilayer. Apparent cholesterol-rich patches are located in specific annular regions next to the transmembrane helices and also in a more extended `microdomain' between the apposed δ subunits of neighbouring receptors. The particular lipid distribution can be interpreted straightforwardly in relation to the gating movements revealed by an earlier time-resolved cryo-EM study, in which the membranes were exposed briefly to ACh. The results suggest that in addition to stabilizing the protein, cholesterol may play a mechanical role by conferring local rigidity to the membrane so that there is productive coupling between the extracellular and membrane domains, leading to opening of the channel.http://scripts.iucr.org/cgi-bin/paper?S2052252517005243nicotinic acetylcholine receptorcholesterollipid microdomaincryo-EMhelical image reconstruction |
| spellingShingle | Nigel Unwin Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM IUCrJ nicotinic acetylcholine receptor cholesterol lipid microdomain cryo-EM helical image reconstruction |
| title | Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM |
| title_full | Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM |
| title_fullStr | Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM |
| title_full_unstemmed | Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM |
| title_short | Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM |
| title_sort | segregation of lipids near acetylcholine receptor channels imaged by cryo em |
| topic | nicotinic acetylcholine receptor cholesterol lipid microdomain cryo-EM helical image reconstruction |
| url | http://scripts.iucr.org/cgi-bin/paper?S2052252517005243 |
| work_keys_str_mv | AT nigelunwin segregationoflipidsnearacetylcholinereceptorchannelsimagedbycryoem |