Expression of the alpha 7 subunit of the nicotinic acetylcholine receptor in normal and myasthenic human thymuses.
The nicotinic acetylcholine receptor (AChR) is a transmembrane glycoprotein composed of five homologous subunits. Different isoforms of the AChR alpha subunit exist (alpha 1 to alpha 9). Of them, alpha 1 is expressed in muscle, alpha 2 to alpha 9 in neuronal cells. Muscle AChR is the target autoantigen in the autoimmune disease myasthenia gravis (MG). The thymus is implicated in MG pathogenesis, and the anti-AChR autoimmune response may start in this tissue, that expresses the muscle-type alpha 1 subunit as well as other muscle AChR subunits. The thymus also expresses the "neuronal" alpha 3 and alpha 5 subunits. By using polymerase chain reaction and other molecular techniques, we demonstrate here expression of the AChR alpha 7 subunit transcript in thymuses from both myasthenic patients and normal subjects. The alpha 7 subunit can form homo-oligomeric functional AChR complexes that, like muscle AChR, bind alpha-bungarotoxin. The demonstration of expression of the alpha 7 subunit in the thymus suggests that alpha-bungarotoxin binding, functional AChRs of the neuronal type are normally present in the thymus.
Navaneetham
D
D
Department of Biochemistry, University of Minnesota, St. Paul 55108, USA.
Penn
A
A
Howard
J
J
Conti-Fine
B M
BM
D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000737:chemistry; D001665:Binding Sites; D002038:Bungarotoxins / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D009132:Muscles / Q000378:metabolism; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D013950:Thymus Gland / Q000378:metabolism*
D001324:Autoantigens; D002038:Bungarotoxins; D012333:RNA, Messenger; D011978:Receptors, Nicotinic