Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear.
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.
Osman
Abdullah A
AA
Department of Otolaryngology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis MO 63110, USA.
Schrader
Angela D
AD
Hawkes
Aubrey J
AJ
Akil
Omar
O
Bergeron
Adam
A
Lustig
Lawrence R
LR
Simmons
Dwayne D
DD
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
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