Dataset

Unraveling the molecular interactions between α7 nicotinic receptor and a RIC3 variant associated with backward speech

Abstract

Recent work putatively linked a rare genetic variant of the chaperone Resistant to Inhibitors of acetylcholinesterase (RIC3) (NM_024557.4:c.262G>A, NP_078833.3:p.G88R) to a unique ability to speak backwards, a language skill that is associated with exceptional working memory capacity. RIC3 is important for the folding, maturation, and functional expression of α7 nicotinic acetylcholine receptors (nAChR). We compared and contrasted the effects of RIC3G88R on assembly, cell surface expression, and function of human α7 receptors using fluorescent protein tagged α7 nAChR and Förster resonance energy transfer (FRET) microscopy imaging in combination with functional assays and 125I-α-bungarotoxin binding. As expected, the wild-type RIC3 protein was found to increase both cell surface and functional expression of α7 receptors. In contrast, the variant form of RIC3 decreased both. FRET analysis showed that RICG88R increased the interactions between RIC3 and α7 protein in the endoplasmic reticulum. These results provide interesting and novel data to show that a RIC3 variant alters the interaction of RIC3 and α7, which translates to decreased cell surface and functional expression of α7 nAChR.

DOI (Digital Object Identifier)

Permanent link to this resource: https://doi.org/10.24384/mp84-n694

Attachments

Authors

Pradhan, A (Oxford Brookes University)
Mountford, H (Oxford Brookes University)
Peixinho, J (Oxford Brookes University)
Rea, E (Oxford Brookes University)
Epeslidou E (University Medical Center Utrecht)
Scott, JS (University Medical Center Utrecht)
Cull, J (Oxford Brookes University)
Maxwell, S (Weatherall Institute of Molecular Medicine)
Webster, R (Weatherall Institute of Molecular Medicine)
Beeson, D (Weatherall Institute of Molecular Medicine)
Dong, Y (Weatherall Institute of Molecular Medicine)
Prekovic, S (University Medical Center Utrecht)
Bermudez, I (Oxford Brookes University)
Newbury, DF (Oxford Brookes University)

Oxford Brookes departments

Department of Biological and Medical Sciences

Dates

Year: 2024

Funding

Leverhulme Trust : Speaking backwards – sdrawkcab gnikaepS (RPG-207-381)
Nigel Groome studentship, Oxford Brookes University : Unravelling the relationship between cigarette smoking and language development
Medical Research Council : Importance of N-glycosylation at the Neuromuscular Junction (MR/S007180/M)
Medical Research Council : Disease mechanisms and therapy for inherited disorders of the neuromuscular synapse. (MR/M006824/1.)

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Published by Oxford Brookes University

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License

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Related resources

This RADAR resource is Cited by Unraveling the molecular interactions between α7 nicotinic receptor and a RIC3 variant associated with backward speech