The fibronectin domains of the neural adhesion molecule TAX-1 are necessary and sufficient for homophilic binding.

Cell adhesion molecules belonging to the immunoglobulin superfamily promote cell aggregation and neurite outgrowth. These proteins are multidomain molecules comprising a number of distinct modules, notably Ig domains of the C2 class and fibronectin type III repeats. A subgroup of these neural adhesion molecules are linked to the membrane with a glycosylphosphatidylinositol anchor and show a more restricted pattern of expression in the embryo. Among them, the human homologue of the transient axonal glycoprotein, named TAX-1, shares a great degree of similarity at the protein level with rodent TAG-1. In the present study we set out to determine which domains of TAX-1 are involved in promoting the homophilic, adhesive properties of the molecule. We established stable Schneider-2 cell lines expressing the intact molecule, the fibronectin, or the immunoglobulin domains. The fibronectin domains were necessary and sufficient to mediate homophilic binding and induce cell aggregation, a response also observed with cells expressing the intact TAX-1 molecule. Aggregation was inhibited by the secreted form of the TAG-1 protein. On the other hand, the immunoglobulin domains by themselves were not able to induce cell aggregation. In addition, TAX-1 was localized in areas of cell contact among aggregating cells, justifying its role as an adhesion molecule.

Isolation of the human MOX2 homeobox gene and localization to chromosome 7p22.1-p21.3.

We have isolated and characterized cDNA clones encoding a novel human homeobox gene, MOX2, the homologue of the murine mox-2 gene. The MOX2 protein contains all of the characteristic features of Mox-2 proteins of other vertebrate species, namely the homeobox, the polyhistidine stretch, and a number of potential serine/threonine phosphorylation sites. The homeodomain of MOX2 protein is identical to all other vertebrate species reported so far (rodents and amphibians). Outside the homeodomain, Mox-2 proteins share a high degree of identity, except for a few amino acid differences encountered between the human and the rodent polypeptides. A polyhistidine stretch of 12 amino acids in the N terminal region of the protein is also conserved among humans, rodents, and (only partly) amphibians. The chromosomal position of MOX2 was assigned to 7p22.1-p21.3.

Isolation of the cDNA and chromosomal localization of the gene (TAX1) encoding the human axonal glycoprotein TAG-1.

The transient axonal glycoprotein (TAG-1) is a cell adhesion molecule that promotes neurite outgrowth and belongs to the immunoglobulin superfamily. We have isolated cDNAs encoding TAX1, the human homologue of TAG-1. Human TAX1 shows a high degree of homology to rat TAX1 and less to its chick counterpart, axonin-1, with 91 and 75% identity at the amino acid level, respectively. The numbers of immunoglobulin (IgC2) domains and fibronectin repeats present in TAG-1 are conserved among the three species. The highest degree of conservation occurs in the second IgC2 domain (98% with the rat and 82% with the chick). The human homologue also contains a putative N-terminal signal sequence and a C-terminal hydrophobic sequence, suggestive of linkage to the cell membrane via phosphatidylinositol. In addition, the two mammalian TAG-1 proteins share the RGD tripeptide, a motif known to mediate recognition of fibronectin by integrins. In situ hybridization to human metaphase chromosomes maps the TAX1 gene encoding human TAG-1 to a single location on chromosome 1q32.