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PHOSPHORYLATED NEUROFILAMENT ANTIGEN REDISTRIBUTION IN INTERCOSTAL NERVE SUBSEQUENT TO RETROGRADE AXONAL-TRANSPORT OF DIPHTHERIA-TOXIN

SUNNER, K; PULLEN, AH; (1995) PHOSPHORYLATED NEUROFILAMENT ANTIGEN REDISTRIBUTION IN INTERCOSTAL NERVE SUBSEQUENT TO RETROGRADE AXONAL-TRANSPORT OF DIPHTHERIA-TOXIN. ACTA NEUROPATHOL , 89 (4) 331 - 340.

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Abstract

A novel enzyme-linked immunosorbent assay technique using specific monoclonal antibodies has been used to examine the proximal-distal distribution of phosphorylated neurofilament proteins (pNF) in normal feline intercostal nerve, and to compare it with that following retrograde axonal transport of the ADP-ribosylating protein diphtheria toxin (DTX) to thoracic motoneurones. The molecular target of DTX is elongation factor 2 which resides solely in the cell body. Normal intercostal nerves exhibited significantly higher amounts of the 200-kDa pNF-H, 160-kDA pNF-M, and 68-kDA pNF-L in proximal nerve than in the distal nerve. The overall content of all three triplet pNF proteins decreased 3 days after injection of DTX, but the normal proximal-distal gradient was retained. By 8 days post DTX injection, the proximal-distal gradient had reversed, with proximal nerve starved of pNF-H and pNF-M and distal nerve showing abnormally high pNF-L content. Correlative immunocytochemistry of spinal cords from normal animals verified that pNF-H and pNF-M are confined to efferent axons in the spinal grey matter, and that motoneurones are only reactive for pNF-L. At 8 days following toxin treatment, motoneurones in the ipsilateral ventral horn were strongly immunoreactive for all pNF. Contralateral motoneurones were non-reactive. Onset of abnormal perikaryal pNF immunoreactivity at 3 days precedes onset of ultrastructural cytopathology. Together these results indicate an early deficit in transference to the axon of NF proteins synthesised prior to full toxicity, probably because of a toxin-induced failure in regulation of phosphorylation-dependent NF assembly and turnover immediately prior to entry into the proximal axon. Results are discussed in relation to diphtheritic motoneuronopathy.

Type:Article
Title:PHOSPHORYLATED NEUROFILAMENT ANTIGEN REDISTRIBUTION IN INTERCOSTAL NERVE SUBSEQUENT TO RETROGRADE AXONAL-TRANSPORT OF DIPHTHERIA-TOXIN
Keywords:MONOCLONAL-ANTIBODIES DISTINGUISH, ADP-RIBOSYLATION, PROTEINS, CYTOSKELETON, INTOXICATION, MOTONEURONES, TRANSECTION, SUBUNITS, NEURONS, SYSTEM
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology

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