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 transc ription factor, but an extracellular protein. We have characterized a highl y 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 carb ohydrates. 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 thi s protein from high molecular mass aggregates. In situ hybridization and im munostaining reveals teneurin-1 expression in neurons of the developing vis ual system of chicken and Drosophila, This phylogenetic conservation of neu ronal 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 encodi ng at least three further members of the teneurin family of proteins. Furth ermore, the human teneurin-1 gene could be identified on chromosome Xq24/25 , a region implied in an X-linked mental retardation syndrome.