title: Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear.
abstract: Nothing is known about the regulation of nicotinic acetylcholine receptors (nAChRs) in hair cells of the inner ear. MuSK, rapsyn and RIC-3 are accessory molecules associated with muscle and brain nAChR function. We demonstrate that these accessory molecules are expressed in the inner ear raising the possibility of a muscle-like mechanism for clustering and assembly of nAChRs in hair cells. We focused our investigations on rapsyn and RIC-3. Rapsyn interacts with the cytoplasmic loop of nAChR alpha9 subunits but not nAChR alpha10 subunits. Although rapsyn and RIC-3 increase nAChR alpha9 expression, rapsyn plays a greater role in receptor clustering while RIC-3 is important for acetylcholine-induced calcium responses. Our data suggest that RIC-3 facilitates receptor function, while rapsyn enhances receptor clustering at the cell surface.
authors.affiliation: Department of Otolaryngology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis MO 63110, USA.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Osman
authors.forename: Angela D
authors.initials: AD
authors.lastname: Schrader
authors.forename: Aubrey J
authors.initials: AJ
authors.lastname: Hawkes
authors.forename: Omar
authors.initials: O
authors.lastname: Akil
authors.forename: Adam
authors.initials: A
authors.lastname: Bergeron
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Lustig
authors.forename: Dwayne D
authors.initials: DD
authors.lastname: Simmons
mesh_terms: D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D018374:LLC-PK1 Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D013569:Synapses / Q000378:metabolism; D014162:Transfection
chemical_list: D002038:Bungarotoxins; C493739:CHRNA10 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C496701:RIC3 protein, human; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; C443079:nAChR alpha9; C051609:peripheral membrane protein 43K; C095714:MUSK protein, human; C511695:MuSK protein, mouse; C475048:MuSK protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D002118:Calcium