The cell adhesion molecule-like tyrosine phosphatase CRYPα is localized on retinal axons and their growth cones. We present evidence that two isoforms of this type IIa phosphatase, CRYPα1 and CRYPα2, have extracellular ligands along the developing retinotectal pathway. Using alkaline phosphatase fusion proteins containing the CRYPα1 ectodomain, we detect a prominent ligand on basement membranes of the early retina, optic stalk, and chiasm. A second ligand is observed in the endfeet region of radial processes in the developing stratum opticum, the site of initial retinal axon invasion. This latter ligand binds CRYPα2 preferentially. Further ligand interactions are detected for both CRYPα protein isoforms in retinorecipient tectal laminae and on retinal fibers themselves. CRYPα thus has cell- and matrix-associated ligands along the entire retinotectal projection. Moreover, these ligands appear to be heterotypic and interact with CRYPα through both its immunoglobulin and fibronectin type III regions. The anteroposterior levels of the ligands are relatively uniform within the retina and tectum, suggesting that the CRYPα protein within retinal axons does not directly recognise topographically graded guidance cues. We propose that CRYPα may have a permissive role in promoting retinal axon growth across the eye and tectum and that its functions are modulated temporally and spatially by isoform-specific interactions with cell- and matrix-associated ligands.
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Developmental Neuroscience