The human-specific nicotinic receptor subunit CHRFAM7A reduces α7 receptor function in human induced pluripotent stem cells-derived and transgenic mouse neurons.

Autor: Görgülü I; Center for Brain Research, Medical University of Vienna, Vienna, Austria., Jagannath V; Institut du Fer à Moulin, Sorbonne University, UMR-S 1270, Paris, France.; MSD R&D Innovation Centre, London, UK., Pons S; Integrative Neurobiology of Cholinergic Systems, Institut Pasteur, Université Paris Cité, UMR 3571, Paris, France., Koniuszewski F; Center for Brain Research, Medical University of Vienna, Vienna, Austria., Groszer M; Institut du Fer à Moulin, Sorbonne University, UMR-S 1270, Paris, France., Maskos U; Integrative Neurobiology of Cholinergic Systems, Institut Pasteur, Université Paris Cité, UMR 3571, Paris, France., Huck S; Center for Brain Research, Medical University of Vienna, Vienna, Austria., Scholze P; Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2024 Sep; Vol. 60 (5), pp. 4893-4906. Date of Electronic Publication: 2024 Jul 28.
DOI: 10.1111/ejn.16474
Abstrakt: We investigated the impact of the human-specific gene CHRFAM7A on the function of α7 nicotinic acetylcholine receptors (α7 nAChRs) in two different types of neurons: human-induced pluripotent stem cell (hiPSC)-derived cortical neurons, and superior cervical ganglion (SCG) neurons, taken from transgenic mice expressing CHRFAM7A. dupα7, the gene product of CHRFAM7A, which lacks a major part of the extracellular N-terminal ligand-binding domain, co-assembles with α7, the gene product of CHRNA7. We assessed the receptor function in hiPSC-derived cortical and SCG neurons with Fura-2 calcium imaging and three different α7-specific ligands: PNU282987, choline, and 4BP-TQS. Given the short-lived open state of α7 receptors, we combined the two orthosteric agonists PNU282987 and choline with the type-2 positive allosteric modulator (PAM II) PNU120596. In line with different cellular models used previously, we demonstrate that CHRFAM7A has a major impact on nicotinic α7 nAChRs by reducing calcium transients in response to all three agonists.
(© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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