PTPmu signaling via PKCdelta is instructive for retinal ganglion cell guidance

The receptor protein tyrosine phosphatase (RPTP) PTPmu mediates distinct cellular responses in nasal and temporal retinal ganglion cell (RGC) axons. PTPmu is permissive for nasal RGC neurite outgrowth and inhibitory to temporal RGCs. In addition, PTPmu causes preferential temporal growth cone collapse. Previous studies demonstrated that PTPmu associates with the scaffolding protein RACK1 and the protein kinase C-delta (PKCdelta) isoform in chick retina and that PKCdelta activity is required for PTPmu-mediated RGC outgrowth. Using in vitro stripe and collapse assays, we find that PKCdelta activity is required for both inhibitory and permissive responses of RGCs to PTPmu, with higher levels of PKCdelta activation associated with temporal growth cone collapse and repulsion. A potential mechanism for differential PKCdelta activation is due to the gradient of PTPmu expression in the retina. PTPmu is expressed in a high temporal, low nasal step gradient in the retina. In support of this, overexpression of exogenous PTPmu in nasal neurites results in a phenotypic switch from permissive to repulsive in response to PTPmu. Together, these results suggest that the differential expression of PTPmu within the retina is instructive for RGC guidance and that the magnitude of PKCdelta activation in response to PTPmu signaling results in the distinct cellular behaviors of nasal and temporal RGCs.