This study presents evidence for retrograde axonal transport of exogenous
albumin and
transferrin in adult brainstem motor neurons, whereas
plasma proteins are not transported in neonatal motor neurons. The
plasma protein uptake in motor neurons was dose-dependent, suggesting a nonspecific (fluid-phase) uptake mechanism. Further evidence for nonspecific uptake of exogenous
transferrin in the motor neuron was found in the presence of
transferrin receptor only on the
soma and not on the axon terminal. The immunoreaction product of the exogenous
plasma proteins was localized as perinuclear granules in association with the lysosomal system, as verified by staining for the lysosomal marker
cathepsin D and by ultrastructural examinations. The results suggest that
albumin and
transferrin derived from hepatic synthesis gain access to motor neurons nonspecifically by retrograde axonal transport, whereas
transferrin derived from intracerebral synthesis specifically gains access to motor neurons due to receptor-mediated uptake at the
soma of the neuron. The lack of
plasma proteins in developing motor neurons suggests that retrograde axonal transport of
plasma proteins has no significance for developing axons.
Plasma proteins have a potential for transporting toxic metals to motor neurons. Intraneuronal uptake of
aluminum-transferrin either by nonspecific uptake in axon terminals or by receptor-mediated uptake at the
soma may have a role in the pathogenesis of the
motor neuron disease amyotrophic lateral sclerosis.