Teneurin-1, a vertebrate homologue of the Drosophila pair-rule gene ten-m, is a neuronal protein with a novel type of heparin-binding domain.
The Drosophila gene ten-m is the first pair-rule gene not encoding a transcription factor, but an extracellular protein. We have characterized a highly conserved chicken homologue that we call teneurin-1. The C-terminal part harbors 26 repetitive sequence motifs termed YD-repeats. The YD-repeats are most similar to the core of the rhs elements of Escherichia coli. Related repeats in toxin A of Clostridium difficile are known to bind specific carbohydrates. We show that recombinantly expressed proteins containing the YD-repeats of teneurin-1 bind to heparin. Furthermore, heparin lyase treatment of extracts of cells expressing recombinant YD-repeat protein releases this protein from high molecular mass aggregates. In situ hybridization and immunostaining reveals teneurin-1 expression in neurons of the developing visual system of chicken and Drosophila. This phylogenetic conservation of neuronal expression from flies to birds implies fundamental roles for teneurin-1 in neurogenesis. This is supported by the neurite outgrowth occurring on substrates made of recombinant YD-repeat proteins, which can be inhibited by heparin. Database searches resulted in the identification of ESTs encoding at least three further members of the teneurin family of proteins. Furthermore, the human teneurin-1 gene could be identified on chromosome Xq24/25, a region implied in an X-linked mental retardation syndrome.
Minet
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Friedrich Miescher Institute, PO Box 2543, CH-4002 Basel, Switzerland.
Rubin
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Tucker
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Baumgartner
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Chiquet-Ehrismann
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R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D019063:Tenascin / Q000235:genetics*
D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D019063:Tenascin; C120530:teneurin-1; D006493:Heparin