{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:56:51Z","timestamp":1791313011974,"version":"4.3.1"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P-11607MED"],"award-info":[{"award-number":["P-11607MED"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P19325-B09"],"award-info":[{"award-number":["P19325-B09"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Synaptic Neurosci."],"abstract":"<jats:p>\n                    Nicotine, the principal reinforcing compound in tobacco, acts in the brain by activating neuronal nicotinic acetylcholine receptors (nAChRs). This review summarizes our current knowledge regarding how the \u03b15 accessory nAChR subunit, encoded by the\n                    <jats:italic>CHRNA5<\/jats:italic>\n                    gene, differentially modulates \u03b14\u03b22\n                    <jats:sup>*<\/jats:sup>\n                    and \u03b13\u03b24\n                    <jats:sup>*<\/jats:sup>\n                    receptors at the cellular level. Genome-wide association studies have linked a gene cluster in chromosomal region 15q25 to increased susceptibility to nicotine addiction, lung cancer, chronic obstructive pulmonary disease, and peripheral arterial disease. Interestingly, this gene cluster contains a non-synonymous single-nucleotide polymorphism (SNP) in the human\n                    <jats:italic>CHRNA5<\/jats:italic>\n                    gene, causing an aspartic acid (D) to asparagine (N) substitution at amino acid position 398 in the \u03b15 nAChR subunit. Although other SNPs have been associated with tobacco smoking behavior, efforts have focused predominantly on the D398 and N398 variants in the \u03b15 subunit. In recent years, significant progress has been made toward understanding the role that the \u03b15 nAChR subunit\u2014and the role of the D398 and N398 variants\u2014plays on nAChR function at the cellular level. These insights stem primarily from a wide range of experimental models, including receptors expressed heterologously in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocytes, various cell lines, and neurons derived from human induced pluripotent stem cells (iPSCs), as well as endogenous receptors in genetically engineered mice and\u2014more recently\u2014rats. Despite providing a wealth of available data, however, these studies have yielded conflicting results, and our understanding of the modulatory role that the \u03b15 subunit plays remains incomplete. Here, we review these reports and the various techniques used for expression and analysis in order to examine how the \u03b15 subunit modulates key functions in \u03b14\u03b22\n                    <jats:sup>*<\/jats:sup>\n                    and \u03b13\u03b24\n                    <jats:sup>*<\/jats:sup>\n                    receptors, including receptor trafficking, sensitivity, efficacy, and desensitization. In addition, we highlight the strikingly different role that the \u03b15 subunit plays in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling between \u03b14\u03b22\n                    <jats:sup>*<\/jats:sup>\n                    and \u03b13\u03b24\n                    <jats:sup>*<\/jats:sup>\n                    receptors, and we discuss whether the N398 \u03b15 subunit variant can partially replace the D398 variant.\n                  <\/jats:p>","DOI":"10.3389\/fnsyn.2020.607959","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T03:29:58Z","timestamp":1606966198000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["The \u03b15 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates \u03b14\u03b22* and \u03b13\u03b24* Receptors"],"prefix":"10.3389","volume":"12","author":[{"given":"Petra","family":"Scholze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigismund","family":"Huck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3389\/fnmol.2020.00072","article-title":"Selective expression of nicotinic receptor sub-unit mRNA in early human fetal forebrain","volume":"13","author":"Alzu'bi","year":"2020","journal-title":"Front. 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