LEUKEMIA INHIBITORY FACTOR AND NERVE GROWTH-FACTOR ARE RETROGRADELY TRANSPORTED AND PROCESSED BY CULTURED RAT SYMPATHETIC NEURONS

How neurons convert the presence of factors at their axon terminals in to signals that affect mechanisms in their cell bodies is unknown, but retrograde axonal transport of the factors themselves may be involved . Nerve growth factor (NGF) and leukemia inhibitory factor (LIF) have previously been shown to produce changes in cell bodies of sympathetic neurons when applied to their peripheral neurites, and it is well est ablished that NGF is retrogradely transported along sympathetic axons. In this study we show that I-125-LIF applied to terminal neurites of rat sympathetic neurons in compartmented cultures is retrogradely tran sported, but at a much lower level compared to the retrograde-transpor t of I-125-NGF. Transport of I-125-LIF was competed by cotreatment wit h unlabeled LIF and was blocked by cotreatment with dinitrophenol. The rate of I-125-LIF transport was independent of NGF concentration. How ever, both I-125-LIF and I-125-NGF transport was reduced by pretreatin g neurons with LIF. SDS-PAGE analysis showed that retrogradely transpo rted radiolabel which accumulated in cell body-containing extracts fol lowing transport of both I-125-LIF and I-125-NGF consisted of intact a s well as partially processed species. Radiolabel also accumulated in the medium bathing the cell bodies and migrated near the dye front on SDS-PAGE, implying that both factors were extensively degraded and rel eased by the neurons. These results are consistent with the suggestion that the retrograde transport of LIF, as thought for NGF, may be impo rtant for retrograde signaling mechanisms. (C) 1994 Academic Press, In c.