CHRFAM7A, a human-specific and partially duplicated α7-nicotinic acetylcholine receptor gene with the potential to specify a human-specific inflammatory response to injury. Issue 2 (3rd December 2014)

• Record Type: Journal Article
• Authors: Costantini, Todd W; Dang, Xitong; Coimbra, Raul; Eliceiri, Brian P; Baird, Andrew
• Is Part Of: Journal of leukocyte biology. Volume 97:Issue 2(2015)
• Page Start: 247
• Page End: 257
• Publication Date: 2014-12-03
• Subjects: neuroinflammation -- vagus nerve -- CHRNA7 -- α7nAChR -- dupα7nAChR -- SLURP1; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4RU0814-381R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Review on the human-specific α 7-nicotinic acetylcholine receptor in leukocytes and human-specialized mechanisms to regulate inflammatory response to injury. Abstract: Conventional wisdom presumes that the α 7nAChR product of CHRNA7 expression mediates the ability of the vagus nerve to regulate the inflammatory response to injury and infection. Yet, 15 years ago, a 2nd structurally distinct and human-specific α 7nAChR gene was discovered that has largely escaped attention of the inflammation research community. The gene, originally called dup α 7nAChR but now known as CHRFAM7A, has been studied exhaustively in psychiatric research because of its association with mental illness. However, dup α 7nAChR/CHRFAM7A expression is relatively low in human brain but elevated in human leukocytes. Furthermore, α 7nAChR research in human tissues has been confounded by cross-reacting antibodies and nonspecific oligonucleotide primers that crossreact in immunoblotting, immunohistochemistry, and RT-PCR. Yet, 3 independent reports show the human-specific CHRFAM7A changes cell responsiveness to the canonical α 7nAChR/CHRNA7 ion-gated channel. Because of its potential for the injury research community, its possible significance to human leukocyte biology, and its relevance to human inflammation, we review the discovery and structure of the dup α 7nAChR/CHRFAM7A gene, the distribution of its mRNA, and its biologic activities and then discuss its possible role(s) in specifying human inflammation and injury. In light of emerging concepts that point to a role for human-specific genes in complex human disease, the existence of a human-specific α 7nAChR regulating inflammatory responses in injury underscores the need for caution in extrapolating findings in the α 7nAChR literature to man. To this end, we discuss the translational implications of a uniquely human α 7nAChR-like gene on new drug target discovery and therapeutics development for injury, infection, and inflammation.