CHRFAM7A alters binding to the neuronal alpha-7 nicotinic acetylcholine receptor.

Neurosci Lett

Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, University of California San Diego Health, 200 W. Arbor Drive #8896, San Diego, CA, 92103, USA. Electronic address:

Published: January 2019

AI Article Synopsis

  • CHRFAM7A is a human-specific gene that alters the formation of the alpha-7 nicotinic acetylcholine receptor, identified through studies using rat cells and transgenic mice models.
  • Experiments show that CHRFAM7A expression decreases the binding of α-bungarotoxin (α-BTX), a protein that usually binds to α7nAchR, indicating this gene interferes with the receptor's function.
  • These findings suggest that understanding CHRFAM7A's role could be significant for human diseases and might open doors for developing targeted therapies.

Article Abstract

Introduction: CHRFAM7A is a uniquely-human gene that encodes a human-specific variant of the alpha-7 nicotinic acetylcholine receptor (α7nAchR). While the homopentameric α7nAChR consists of 5 equal subunits, previous studies demonstrated that CHRFAM7A expression disrupts the formation of α7nAChR homopentamers. Here we use a rat neuronal cell line expressing CHRFAM7A and a transgenic mouse expressing CHRFAM7A to define the alpha-bungarotoxin (α-BTX) binding in vitro and in vivo.

Methods: Rat PC12 cells were stably transfected with human CHRFAM7A. α-BTX, a protein that irreversibly binds the α7nAchR, was utilized to assess the capacity for CHRFAM7A to interfere with α 7AchR subunits using immunohistochemistry and flow cytometry. To evaluate the effects of CHRFAM7A on α7nAchR at the neuromuscular junction in vivo, transgenic mice were engineered to express the uniquely human gene CHRFAM7A under the control of the EF1-α promoter. Using this model, muscle was harvested and CHRFAM7A and CHRNA7 gene expression evaluated by PCR. Binding of α-BTX to the α7nAchR in muscle was compared in sibling-matched wild-type C57 mice by immunostaining the neuromuscular junction using α-BTX and neurofilament antibodies.

Results: Expression of CHRFAM7A in transfected, but not vector cells, was confirmed by PCR and by immunoblotting using an antibody we raised to a peptide sequence unique to CHRFAM7A. CHRFAM7A decreased α-BTX binding as detected by immunohistochemistry and flow cytometry. In vivo, α-BTX co-stained with neurofilament at the neuromuscular junction in wild-type mice, however, α-BTX staining was decreased at the neuromuscular junction of CHRFAM7A transgenic mice.

Conclusion: CHRFAM7A expression interferes with the binding of α7nAchR to α-BTX. Understanding the contribution of this uniquely human gene to human disease will be important in the identification of potential therapeutic targets.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320298PMC
http://dx.doi.org/10.1016/j.neulet.2018.10.010DOI Listing

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