Retinotectal ligands for the receptor tyrosine phosphatase CRYP alpha

The cell adhesion molecule-like tyrosine phosphatase CRYP alpha is localize d on retinal axons and their growth cones. We present evidence that two iso forms of this type IIa phosphatase, CRYP alpha 1 and CRYP alpha 2, have ext racellular ligands along the developing retinotectal pathway. Using alkalin e phosphatase fusion proteins containing the CRYP alpha 1 ectodomain, we de tect a prominent ligand on basement membranes of the early retina, optic st alk, and chiasm. A second ligand is observed in the endfeet region of radia l processes in the developing stratum opticum, the site of initial retinal axon invasion. This latter ligand binds CRYP alpha 2 preferentially. Furthe r ligand interactions are detected for both CRYP alpha protein isoforms in retinorecipient tectal laminae and on retinal fibers themselves. CRYP alpha thus has cell- and matrix-associated ligands along the entire retinotectal projection. Moreover, these ligands appear to be heterotypic and interact with CRYP alpha through both its immunoglobulin and fibronectin type III re gions. The anteroposterior levels of the ligands are relatively uniform wit hin the retina and tectum, suggesting that the CRYP alpha protein within re tinal axons does not directly recognise topographically graded guidance cue s. We propose that CRYP alpha may have a permissive role in promoting retin al axon growth across the eye and tectum and that its functions are modulat ed temporally and spatially by isoform-specific interactions with cell- and matrix-associated ligands.