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

The mRNAs for heat shock protein 90 (HSP90) are found at highest levels (di fferentially expressed) in the primate retinal fovea, the region of highest visual acuity, compared to the peripheral retina. HSP90 expression and ret inal associations were analyzed by immuno-localization, in situ hybridizati on, and western analysis. Retinal ganglion cells (RGCs) express much of the HSP90 mRNA present in the primate retinal fovea. A large fraction of RGC s ynthesized HSP90 is apparently present in the axonal compartment. To identi fy the role of HSP90 protein in the optic nerve and retina, co-immunoprecip itation experiments were performed, using antibodies specific for HSP90 iso forms. The immunoprecipitates were analyzed for neurotrophin receptor and l igand activities, and MAP kinase activity. MAP kinase assay was used to det ermine the activation state of MAP kinase associated with HSP90. HSP90 prot eins selectively associate with the inactive form of full-length tyrosine k inase growth factor receptor trkB, suggesting utilization during anterograd e axonal transport. Activated MAP kinase, associated with the trk downstrea m signaling cascade, was found to co-immunoprecipitate with optic nerve HSP 90, suggesting that HSP90 may be utilized in retrograde transport of the se condary messengers associated with neurotrophin signaling. HSP90 can thus b e hypothesized to play a role in bidirectional RGC axonal protein transport .