Heat shock protein 90 in retinal ganglion cells: Association with axonally transported proteins

The mRNAs for heat shock protein 90 (HSP90) are found at highest levels (differentially expressed) in the primate retinal fovea, the region of highest visual acuity, compared to the peripheral retina. HSP90 expression and retinal associations were analyzed by immuno-localization, in situ hybridization, and western analysis. Retinal ganglion cells (RGCs) express much of the HSP90 mRNA present in the primate retinal fovea. A large fraction of RGC synthesized HSP90 is apparently present in the axonal compartment. To identify the role of HSP90 protein in the optic nerve and retina, co-immunoprecipitation experiments were performed, using antibodies specific for HSP90 isoforms. The immunoprecipitates were analyzed for neurotrophin receptor and ligand activities, and MAP kinase activity. MAP kinase assay was used to determine the activation state of MAP kinase associated with HSP90. HSP90 proteins selectively associate with the inactive form of full-length tyrosine kinase growth factor receptor trkB, suggesting utilization during anterograde axonal transport. Activated MAP kinase, associated with the trk downstream signaling cascade, was found to co-immunoprecipitate with optic nerve HSP90, suggesting that HSP90 may be utilized in retrograde transport of the secondary messengers associated with neurotrophin signaling. HSP90 can thus be hypothesized to play a role in bidirectional RGC axonal protein transport.