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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Bungarotoxins / pharmacology
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Calcium / metabolism
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Female
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Hair Cells, Auditory, Inner / cytology
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Hair Cells, Auditory, Inner / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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Kidney / cytology
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LLC-PK1 Cells
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Male
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Mice
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Mice, Inbred C57BL
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Muscle Proteins / metabolism*
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Pregnancy
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptor Protein-Tyrosine Kinases / genetics*
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptors, Cholinergic / genetics
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Receptors, Cholinergic / metabolism
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Receptors, Nicotinic / genetics
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Receptors, Nicotinic / metabolism*
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Swine
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Synapses / metabolism
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Transfection
Substances
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Bungarotoxins
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CHRNA10 protein, human
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Intracellular Signaling Peptides and Proteins
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Muscle Proteins
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RIC3 protein, human
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RNA, Messenger
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Receptors, Cholinergic
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Receptors, Nicotinic
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nAChR alpha9
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peripheral membrane protein 43K
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MUSK protein, human
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MuSK protein, mouse
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MuSK protein, rat
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Receptor Protein-Tyrosine Kinases
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Calcium