Altered Axonal Transport of Cytoskeletal Proteins in the Mutant Diabetic Mouse

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Abstract
Polypeptides in the motor axons of the sciatic nerve in 120-day-old normal and diabetic mice C57BL/Ks (db/db) were labeled by injection of [35S]methionine into the ventral horn of the spinal cord. At 8, 15 and 25 days after the injection, the distribution of radiolabeled polypeptides along the sciatic nerve as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Four major radiolabeled polypeptides, tentatively identified as actin, tubulin and the 2 lightest subunits of the neurofilament triplet, were studied in both diabetic and control mice. In the diabetic animals, the 2 polypeptides identified as actin and tubulin showed a reduction of average velocity of migration along the sciatic nerve, resulting in a higher fraction of radioactivity in the proximal part of the sciatic nerve, whereas the front of radioactivity (advancing at maximal velocity) moved at a normal rate. In contrast, both the average and maximal velocities of the two neurofilament subunits were slower in the diabetic mice than in the control mice. The axonal transport of the cytoskeletal proteins is differentially affected in the course of diabetic neuropathy, and may sugggest that the impairment concerns manly the proteins carried by the slowest component of axonal transport.