Variants and exons of the glyt1 transporter

Abstract

The present invention provides polypeptide and polynucleotide sequences for novel splice variants of the sodium and chloride-dependent glycine transporter type 1 (GlyT1). These polypeptides and polynucleotides are useful in the treatment and diagnosis of disorders such as neurological and psychiatric disorders including schizophrenia. The invention also provides antibodies directed specifically against these novel polypeptides, and kits comprising the herein-described polynucleotides, polypeptides, and/or antibodies.

1 . An isolated, purified, or recombinant polynucleotide comprising:
 a) SEQ ID NOs:2-9 or 14-19 or 21, or a sequence complementary to any of these sequences;   b) a nucleic acid sequence having at least about 95% identity to SEQ ID NOs: 14-19 or 21 and encoding a functional glycine transporter; or   c) a polynucleotide which encodes a polypeptide comprising SEQ ID NOs:26-31 or 33.   
     
     
         2 . The polynucleotide of  claim 1 , wherein said polynucleotide is attached to a solid support. 
     
     
         3 . The polynucleotide of  claim 1 , further comprising a label. 
     
     
         4 . The polynucleotide of  claim 1 , wherein said polynucleotide is operably linked to a promoter. 
     
     
         5 . An array of polynucleotides comprising the polynucleotide of  claim 1 . 
     
     
         6 . The array of  claim 5 , wherein said array is addressable. 
     
     
         7 . A recombinant vector comprising the polynucleotide of  claim 1 . 
     
     
         8 . A host cell comprising the recombinant vector of  claim 7 . 
     
     
         9 . A non-human host animal or mammal comprising the recombinant vector of  claim 7 . 
     
     
         10 . An isolated, purified, or recombinant polypeptide comprising:
 a) SEQ ID NOs:26-33; or   b) the polypeptide encoded by any of the nucleic acid sequences shown as SEQ ID NOs:2-9 or 14-21.   
     
     
         11 . A method of producing a GlyT1 polypeptide, said method comprising the following steps:
 a) providing a host cell comprising a nucleic acid according to  claim 1  operably linked to a promoter;   b) cultivating said host cell under conditions conducive to the expression of said polypeptide; and   c) isolating said polypeptide from said host cell.   
     
     
         12 . An isolated or purified antibody capable of selectively binding to an epitope-containing fragment of a polypeptide according to  claim 10 . 
     
     
         13 . A method of binding an anti-GlyT1 antibody to a polypeptide comprising contacting said antibody with said polypeptide according to  claim 10  under conditions in which said antibody can specifically bind to said polypeptide. 
     
     
         14 . A diagnostic kit comprising a polynucleotide according to  claim 1 . 
     
     
         15 . A method of detecting the expression of a GlyT1 gene within a cell, said method comprising the steps of:
 a) contacting said cell or an extract from said cell with a polynucleotide that hybridizes under stringent conditions to a polynucleotide encoding GlyT1 or a compound that specifically binds to GlyT1; and   b) detecting the presence or absence of hybridization between said polynucleotide and an RNA species within said cell or extract, or the presence or absence of binding of said compound to a protein within said cell or extract;   
       wherein a detection of the presence of said hybridization or of said binding indicates that said GlyT1 gene is expressed within said cell. 
     
     
         16 . The method of  claim 15 , wherein said polynucleotide is an oligonucleotide primer, and wherein said hybridization is detected by detecting the presence of an amplification product comprising the sequence of said primer. 
     
     
         17 . The method of  claim 15 , wherein said compound is an anti-GlyT1 antibody. 
     
     
         18 . A method of identifying a candidate modulator of a GlyT1 polypeptide, said method comprising:
 a) contacting the polypeptide of  claim 10  with a test compound; and   b) determining whether said compound specifically binds to said polypeptide;   
       wherein a detection that said compound specifically binds to said polypeptide indicates that said compound is a candidate modulator of said GlyT1 polypeptide. 
     
     
         19 . The method of  claim 18 , further comprising testing the activity of said GlyT1 polypeptide in the presence of said candidate modulator, wherein a difference in the activity of said GlyT1 polypeptide in the presence of said candidate modulator in comparison to the activity in the absence of said candidate modulator indicates that the candidate modulator is a modulator of said GlyT1 polypeptide. 
     
     
         20 . A method of identifying a modulator of a GlyT1 polypeptide, said method comprising:
 a) contacting the polypeptide of  claim 10  with a test compound; and   b) detecting the activity of said polypeptide in the presence and absence of said compound;   
       wherein a detection of a difference in said activity in the presence of said compound in comparison to the activity in the absence of said compound indicates that said compound is a modulator of said GlyT1 polypeptide. 
     
     
         21 . The method of  claim 19 , wherein said polypeptide is present in a cell or cell membrane, and wherein said activity comprises glycine transport activity. 
     
     
         22 . The method of  claim 20 , wherein said polypeptide is present in a cell or cell membrane, and wherein said activity comprises glycine transport activity. 
     
     
         23 . A method for pharmaceutical composition comprising:
 a) identifying a modulator of a GlyT1 polypeptide using the method of  claim 20 ; and   b) combining said modulator with a physiologically acceptable carrier.