CHRFAM7A, a human‐specific and partially duplicated α7‐nicotinic acetylcholine receptor gene with the potential to specify a human‐specific inflammatory response to injury

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: neuroinflammation;    vagus nerve;    CHRNA7;    α;    7nAChR;    dupα;    7nAChR;    SLURP1;   

DOI  :  10.1189/jlb.4RU0814-381R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Conventionalwisdompresumesthattheα7nAChRproductofCHRNA7expressionmediatestheabilityofthevagusnervetoregulatetheinflammatoryresponsetoinjuryandinfection.Yet,15yearsago,a2ndstructurallydistinctandhuman‐specificα7nAChRgenewasdiscoveredthathaslargelyescapedattentionoftheinflammationresearchcommunity.Thegene,originallycalleddupα7nAChRbutnowknownasCHRFAM7A,hasbeenstudiedexhaustivelyinpsychiatricresearchbecauseofitsassociationwithmentalillness.However,dupα7nAChR/CHRFAM7Aexpressionisrelativelylowinhumanbrainbutelevatedinhumanleukocytes.Furthermore,α7nAChRresearchinhumantissueshasbeenconfoundedbycross‐reactingantibodiesandnonspecificoligonucleotideprimersthatcrossreactinimmunoblotting,immunohistochemistry,andRT‐PCR.Yet,3independentreportsshowthehuman‐specificCHRFAM7Achangescellresponsivenesstothecanonicalα7nAChR/CHRNA7ion‐gatedchannel.Becauseofitspotentialfortheinjuryresearchcommunity,itspossiblesignificancetohumanleukocytebiology,anditsrelevancetohumaninflammation,wereviewthediscoveryandstructureofthedupα7nAChR/CHRFAM7Agene,thedistributionofitsmRNA,anditsbiologicactivitiesandthendiscussitspossiblerole(s)inspecifyinghumaninflammationandinjury.Inlightofemergingconceptsthatpointtoaroleforhuman‐specificgenesincomplexhumandisease,theexistenceofahuman‐specificα7nAChRregulatinginflammatoryresponsesininjuryunderscorestheneedforcautioninextrapolatingfindingsintheα7nAChRliteraturetoman.Tothisend,wediscussthetranslationalimplicationsofauniquelyhumanα7nAChR‐likegeneonnewdrugtargetdiscoveryandtherapeuticsdevelopmentforinjury,infection,andinflammation...

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