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dc.contributor.authorMesoey, Susanne
dc.contributor.authorBridgland-Taylor, Matthew
dc.contributor.authorLummis, Sarah
dc.date.accessioned2022-05-18T15:00:40Z
dc.date.available2022-05-18T15:00:40Z
dc.date.issued2022
dc.date.submitted2022-01-08
dc.identifier.issn1664-042X
dc.identifier.other850782
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337270
dc.description.abstractThe role of the outermost helix (M4) in the pentameric ligand-gated ion channel (pLGIC) family is currently not fully understood. It is known that M4 is important for receptor assembly, possibly via interactions with neighboring M1 and M3 helices. M4 can also transmit information on the lipid content of the membrane to the gating mechanism, and it may form a link to the extracellular domain via the Cys-loop. Our previous study examining the α4β2 nACh receptor M4 helix using HEK cells indicated M4 here is more sensitive to change than those of other pLGIC. Many of these other studies, however, were performed in Xenopus oocytes. Here we examine the nine previously identified nonfunctional α4β2 nACh receptor M4 mutant receptors using this system. The data reveal that seven of these mutant receptors do function when expressed in oocytes, with only 2, the conserved Asp at the intracellular end of M4 and a Phe in the center, having a similar phenotype (nonfunctional) in both HEK cells and oocytes. The oocyte data are more consistent with studies in other pLGIC and demonstrate the importance of the expression system used. Of the many differences between these two expression systems, we suggest that the different lipid content of the plasma membrane is a possible candidate for explaining these discrepancies.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectPhysiology
dc.subjectCys-loop receptor
dc.subjectM4
dc.subjectmutagenesis
dc.subjectaromatic interaction
dc.subjectnACh receptor
dc.titleMutations of the nACh Receptor M4 Helix Reveal Different Phenotypes in Different Expression Systems: Could Lipids be Responsible?
dc.typeArticle
dc.date.updated2022-05-18T15:00:40Z
prism.publicationNameFront Physiol
prism.volume13
dc.identifier.doi10.17863/CAM.84685
dcterms.dateAccepted2022-03-31
rioxxterms.versionofrecord10.3389/fphys.2022.850782
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMesoey, Susanne [0000-0001-7497-9985]
dc.contributor.orcidLummis, Sarah [0000-0001-9410-9805]
dc.identifier.eissn1664-042X
pubs.funder-project-idMedical Research Council (MR/L021676/1)
cam.issuedOnline2022-05-04


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