Retrograde axonal transport of the alpha subunit of the GTP-binding protein Gz to the nucleus of sensory neurons.

Nerve cells are exquisitely sensitive to target tissue derived factors and the discovery that nerve growth factor could be retrogradely transported in axons suggested that the physical translocation of proteins along the axon could be a mechanism to convey this signal. This message is not due to the neurotrophic factor itself but rather due to second messengers generated by interaction with receptors. We have previously demonstrated the retrograde axonal transport of the alpha subunits of two putative second messenger molecules Gi and Gz. We have investigated more thoroughly the transport of the alpha subunit of Gz (Gz alpha) and in order to be more certain that the immunoreactivity seen is due to Gz alpha, we have made antibodies to peptides from both the N- and C-terminal regions of Gz alpha, which recognise the same 41 kDa band on Western blots of brain and sciatic nerve extracts. This band is eliminated when the antibodies are previously incubated with the specific peptide to which they were made. Using these antibodies for immunohistochemical localisation for Gz alpha, we now report that the GTP-binding protein Gz, is not only retrogradely transported in axons but that it translocates to the neuronal nucleus. Furthermore, the levels seen in the nuclear compartment decline after axotomy or ligation of the mice under ether anaesthetic, suggesting it is the retrogradely transported Gz alpha that is accumulating in the nucleus after activation at the nerve terminal.