Eukaryotic mechanosensory transduction channel
AssigneeThe Regents of the University of California
InventorsCharles S. Zuker, Richard G. Walker, Aarron Willingham
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Abstract
The present invention provides, for the first time, nucleic acids encoding a eukaryotic mechanosensory transduction channel (MSC) protein. The proteins encoded by these nucleic acids form channels that can directly detect mechanical stimuli and convert them into electrical signals. These nucleic acids and the proteins they encode can be used as probes for sensory cells in animals, and can be used to diagnose and treat any of a number of human conditions involving inherited, casual, or environmentally-induced loss of mechanosensory transduction activity.
Claims26
An isolated nucleic acid encoding a mechanosensory transduction protein, the protein having at least one of the following characteristics:
- (i) comprising greater than about 70% amino acid sequence identity to SEQ ID NO:2 or SEQ ID NO:4;
- (ii) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9;
- or
- (iii) specifically binding to polyclonal antibodies generated against a polypeptide comprising an amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4;
- wherein the protein does not comprise the amino acid sequence of SEQ ID NO:6.
An isolated nucleic acid encoding an extracellular domain of a mechanosensory transduction protein, the extracellular domain comprising greater than about 70% amino acid sequence identity to an extracellular domain of SEQ ID NO:2 or SEQ ID NO:4, wherein the extracellular domain does not comprise an extracellular domain of SEQ ID NO:6.
An isolated mechanosensory transduction protein, the protein having at least one of the following characteristics:
- (i) comprising greater than about 70% amino acid sequence identity to SEQ ID NO:2 or SEQ ID NO:4;
- (ii) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9;
- or
- (iii) specifically binding to polyclonal antibodies generated against a polypeptide comprising an amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4;
- wherein the protein does not comprise the amino acid sequence of SEQ ID NO:6.
An isolated polypeptide comprising an extracellular domain of a mechanosensory transduction protein, the extracellular domain comprising greater than about 70% amino acid sequence identity to an extracellular domain of SEQ ID NO:2 or SEQ ID NO:4, wherein the extracellular domain does not comprise the amino acid sequence of an extracellular domain of SEQ ID NO:6.
An antibody that selectively binds to a mechanosensory transduction protein, the protein having at least one of the following characteristics:
- (i) comprising greater than about 70% amino acid sequence identity to SEQ ID NO:2 or SEQ ID NO:4;
- (ii) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9;
- or
- (iii) specifically binding to polyclonal antibodies generated against a polypeptide comprising an amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4;
- wherein the protein does not comprise the amino acid sequence of SEQ ID NO:6.
A method for identifying a compound that modulates mechanosensory receptor activity in eukaryotic cells, the method comprising the steps of:
- (i) contacting the compound with a mechanosensory receptor protein, the protein having at least one of the following characteristics:
- (a) comprising greater than about 70% amino acid sequence identity to a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:6;
- (b) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9;
- or
- (c) specifically binding to polyclonal antibodies generated against a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:6;
- and
- (ii) determining the functional effect of the compound on the mechanosensory receptor protein.
A method of genotyping a human for a mechanosensory transduction channel locus, the method comprising detecting a mutation in a nucleic acid encoding a mechanosensory transduction protein in the human, the protein having at least one of the following characteristics:
- (a) comprising greater than about 70% amino acid sequence identity to a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:6;
- (b) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9;
- or
- (c) specifically binding to polyclonal antibodies generated against a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:6;
- wherein the mutation introduces a premature stop codon into the nucleic acid upstream of the region encoding the transmembrane domain region of the protein, or is a missense mutation removing a cysteine residue between transmembrane segments 4 and 5 of the protein.
Dependencies are inferred from the claim text.