Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion.
Am. J. Pathol. 157, 1377-1391 (2000)[PubMed:11021840]
Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous blistering disease. It was assumed that PV is caused by anti-desmoglein (Dsg) 3 autoimmunity because absorption of PV sera with a chimeric baculoprotein containing the Dsg 3 and IgG1 portions, rDsg3-Ig-His, eliminated disease-causing antibodies. In this study we demonstrate that rDsg3-Ig-His adsorbs out autoantibodies to different keratinocyte antigens, including a non-Dsg 3 130-kd polypeptide. Because the pool of disease-causing PV IgGs contains antibodies against the keratinocyte acetylcholine receptor (AChR), we sought to identify the targeted receptor(s). Preincubation of monkey esophagus with PV antibodies blocked specific staining of the keratinocyte cell membrane with rabbit monoepitopic antibody to alpha9 AChR, indicating that this first of its kind AChR with dual, muscarinic and nicotinic pharmacology is targeted by PV autoimmunity. Anti-alpha9 antibody stained keratinocytes in a fishnet-like intercellular pattern, and visualized a single band at approximately 50 kd in Western blots of keratinocyte membrane proteins. Using step-by-step reverse transcription polymerase chain reactions with primers based on known alpha9 sequence regions, we identified the complete reading frame of human alpha9. Its amino acid sequence showed 85% similarity with rat alpha9. Treatment of keratinocyte monolayers with anti-alpha9 antibody induced pemphigus-like acantholysis, which could be reversed either spontaneously or by using the cholinergic agonist carbachol. We conclude that alpha9 is coupled to physiological regulation of keratinocyte adhesion, and its interaction with PV IgG may lead to blister development.
We present herein the cloning of the human nicotinic acetylcholine receptor alpha9-ortholog and the identification of a new alpha-like subunit (alpha10) that shares 58% identity with alpha9. Whereas alpha10 fails to produce functional receptors alone, it promoted robust acetylcholine-evoked currents when coinjected with alpha9. The presence of alpha10 modifies the physiological and pharmacological properties of the alpha9 receptor indicating that the two subunits coassemble in a single functional receptor. Fusing the N-terminal domain of alpha9 with the rest of the alpha10-cDNA yielded a functional alpha9:alpha10-chimera that displays the acetylcholine binding properties of alpha9 and ionic pore characteristics of alpha10-containing receptors. In addition, alpha9- and alpha10-subunit mRNAs show limited similar tissue distribution patterns and are expressed in cochlea, pituitary gland, and keratinocytes. These data suggest that, in vivo, alpha9-containing receptors coassemble with alpha10-subunit.
Catalysis of facilitated diffusion of a calcium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
IEAUniProtKB KW
GO biological process
Detection of mechanical stimulus involved in sensory perception of sounddefinition[GO:0050910]‹silver
The series of events involved in the perception of sound vibration. The vibration is received by a cell and converted into a molecular signal.
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.
The process in which the anatomical structures of the inner ear are generated and organized. The inner ear is the structure in vertebrates that contains the organs of balance and hearing. It consists of soft hollow sensory structures (the membranous labyrinth) containing fluid (endolymph) surrounded by fluid (perilymph) and encased in a bony cavity (the bony labyrinth). It consists of two chambers, the sacculus and utriculus, from which arise the cochlea and semicircular canals respectively.
IEAOrtholog Compara
Pathways
According to KEGG, this protein belongs to the following pathway:
Protein involved in the transport of calcium ions. Calcium is essential for a variety of bodily functions, such as neurotransmission, muscle contraction and proper heart function.
Protein involved in the transport of ions. Such proteins are usually transmembrane and mediate a movement of ions across cell membranes. Transport may be passive (facilitated diffusion; down the electrochemical gradient), or active (against the electrochemical gradient). Active transport requires energy which may come from light, oxidation reactions, ATP hydrolysis, or cotransport of other ions or molecules.
Protein involved in the transport of a molecule (metabolite, protein, etc), a ion or an electron across cell membranes, inside the cell or in a tissue fluid.
Cell membrane glycoprotein forming a channel in a biological membrane selectively permeable to calcium ions. Calcium is essential for a variety of bodily functions, such as neurotransmission, muscle contraction and proper heart function.
Protein which is part of a transmembrane protein complex that forms a hydrophilic channel across the lipid bilayer through which specific inorganic ions can diffuse down their electrochemical gradients. The channels are usually gated and only open in response to a specific stimulus, such as a change in membrane potential (voltage-gated) or the binding of a ligand (ligand-gated channel).
Protein which forms or is a component of a ligand-gated channel. Ligand-gated channels are transmembrane ion channels whose permeability is increased by the binding of a specific ligand, such as neurotransmitters, ionositol triphosphates, and cyclic nucleotides.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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