Novel Semaphorin gene: Semaphorin Y

Abstract

The present invention provides Semaphorin Y inhibiting neurite outgrowth, and a gene therefor, as well as other Semaphorins hybridizing to said Semaphorin Y gene, modified proteins or partial peptides of said Semaphorin Y, antibodies against said Semaphorin Y, antisense nucleotides against said Semaphorin Y gene, and the use of such substances as pharmaceutical or diagnostic agents or laboratory reagents. The present invention further provides a method of screening for Semaphorin Y antagonists employing said Semaphorin Y, Semaphorin Y antagonists obtained by said screening method, pharmaceutical agents comprising such antagonists, and transgenic animals involving said Semaphorin Y.

1 . An isolated polypeptide comprising the amino acid sequence shown in SEQ ID No: 3.  
     
     
         2 . An isolated polypeptide comprising the amino acid sequence shown in SEQ ID NO: 6.  
     
     
         3 . A polypeptide obtained by expressing in a cell a nucleic acid comprising a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence of SEQ ID NO: 1,    (b) the nucleotide sequence of SEQ ID NO: 2,    (c) the nucleotide sequence of SEQ ID NO: 4,    (d) the nucleotide sequence of SEQ ID NO: 5,    (e) a cDNA sequence encoding the amino acid sequence of SEQ ID NO:3, and    (f) a cDNA sequence encoding the amino acid sequence of SEQ ID NO: 6.    
     
     
         4 . A polypeptide obtained by expressing in a cell a nucleic acid comprising a cDNA that 
 i) specifically hybridizes to the antisense strand of the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 4 or SEQ ID NO: 5 under hybridization conditions of a buffer comprising 45%(v/v) formamide, 5×SSPE at 42° C., and washing after hybridization with a buffer comprising 2×SSPE at 55° C.; and    ii) encodes a protein having biological activity of inhibiting neurite outgrowth of neurons of the peripheral nervous system or of collapsing growth cones of neurons of the peripheral nervous system or both.    
     
     
         5 . The polypeptide according to  claim 4 , wherein said nucleic acid originates from a mammal.  
     
     
         6 . An isolated polypeptide comprising six or more contiguous amino acids of SEQ ID NO: 3.  
     
     
         7 . An isolated polypeptide comprising six or more contiguous amino acids of SEQ ID NO: 6.  
     
     
         8 . A method for screening for an antagonist of Semaphorin Y, comprising the steps of: 
 adding a polypeptide comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 6 to an assay system for Semaphorin Y activity, and    adding a test substance to said assay system, and    assaying for Semaphorin Y activity of collapsing growth cones of neurons,    wherein inhibition of the Semaphorin Y activity which results from the addition of the test substance indicates that said test substance is an antagonist of Semaphorin Y.    
     
     
         9 . A method for screening for an antagonist of Semaphorin Y, comprising the steps of: 
 adding a polypeptide according to  claim 3  or  claim 4  to an assay system for Semaphorin Y activity, and    adding a test substance to said assay system, and    assaying for Semaphorin Y activity of collapsing growth cones of neurons,    wherein inhibition of the Semaphorin Y activity which results from the addition of the test substance indicates that said test substance is an antagonist of Semaphorin Y.