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Volume 17, Number 4, Issue of February 15, 1997 pp. 1282-1290
Copyright ©1997 Society for Neuroscience

Retrograde Transport and Steady-State Distribution of ¹²⁵I-Nerve Growth Factor in Rat Sympathetic Neurons in Compartmented Cultures

Received Sept. 9, 1996; revised Nov. 18, 1996; accepted Dec. 3, 1996.

Daren R. Ure and Robert B. Campenot

Department of Cell Biology and Anatomy, University of Alberta, Edmonton, Alberta, Canada T6G 2H7

We have used compartmented cultures of rat sympathetic neurons to quantitatively examine the retrograde transport of ¹²⁵I-nerve growth factor (NGF) supplied to distal axons and to characterize the cellular events that maintain steady-state levels of NGF in cell bodies. In cultures allowed to reach steady-state ¹²⁵I-NGF transport, cell bodies contained only 5-30% of the total neuron-associated ¹²⁵I-NGF, whereas 70-95% remained associated with the distal axons. This was true over an 8 pM to 1.5 nM ¹²⁵I-NGF concentration range, indicating that saturation of high affinity receptors could not account for the large fraction of ¹²⁵I-NGF remaining in axons. Dissociation assays indicated that 85% of ¹²⁵I-NGF associated with distal axons was surface-bound. At steady-state, only 2-25% of the distal axon-associated ¹²⁵I-NGF was retrogradely transported each hour, with higher transport rates associated with younger cultures and lower ¹²⁵I-NGF concentrations. The velocity of ¹²⁵I-NGF retrograde transport was estimated at 10-20 mm/hr. However, as in a previous report, almost no ¹²⁵I-NGF transport was observed during the first hour after ¹²⁵I-NGF administration, indicating a significant lag between receptor binding and loading onto the retrograde transport system. During ¹²⁵I-NGF transport through axons spanning an intermediate compartment in five-compartment cultures, little or no ¹²⁵I-NGF was degraded or released from the axons. After transport, ¹²⁵I-NGF was degraded with a half-life of 3 hr. In summary, although some cellular events promoted NGF accumulation in cell bodies, distal axons represented by far the principal site of NGF-receptor interaction at steady-state as a result of a low retrograde transport rate.

Key words: nerve growth factor; retrograde transport; sympathetic neurons; axon; degradation; endocytosis; retroendocytosis

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