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The human-specific nicotinic receptor subunit CHRFAM7A reduces α7 nAChR function in human iPSC-derived and transgenic mouse neurons
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  • Ilayda Görgülü,
  • Vinita Jagannath,
  • Stephanie Pons,
  • Filip Koniuszewski,
  • Matthias Groszer,
  • Uwe Maskos,
  • Sigismund Huck,
  • Petra Scholze
Ilayda Görgülü
Medical University of Vienna
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Vinita Jagannath
Institut du Fer à Moulin
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Stephanie Pons
Institut Pasteur
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Filip Koniuszewski
Medical University of Vienna
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Matthias Groszer
Institut du Fer à Moulin
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Uwe Maskos
Institut Pasteur
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Sigismund Huck
Medical University of Vienna
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Petra Scholze
Medical University of Vienna

Corresponding Author:petra.scholze@meduniwien.ac.at

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Abstract

We investigated the impact of the human-specific protein CHRFAM7A (also referred to as “dupα7”) on the function of α7 nicotinic acetylcholine receptors (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. CHRFAM7A co-assembles with α7 (also referred to as CHRNA7) but lacks a major part of the extracellular N-terminal ligand-binding domain. We assessed the function of α7 in these preparations 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 with the type-2 positive allosteric modulator (PAM II) PNU120596. In line with different cellular models used previously we demonstrate in primary human iPS-derived and in mouse neurons that CHRFAM7A has a major impact on nicotinic α7 receptors by reducing calcium transients in response to all three agonists.
Submitted to European Journal of Neuroscience
30 Apr 2024Editorial Decision: Revise Minor
08 Jun 20241st Revision Received
14 Jun 2024Submission Checks Completed
14 Jun 2024Review(s) Completed, Editorial Evaluation Pending
14 Jun 2024Assigned to Editor
14 Jun 2024Reviewer(s) Assigned
08 Jul 2024Editorial Decision: Accept