Early Effects of β,β′-Iminodipropionitrile on Tubulin Solubility and Neurofilament Phosphorylation in the Axon
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 63, Issue 1, pages 291–300, July 1994
How to Cite
Tashiro, T., Imai, R. and Komiya, Y. (1994), Early Effects of β,β′-Iminodipropionitrile on Tubulin Solubility and Neurofilament Phosphorylation in the Axon. Journal of Neurochemistry, 63: 291–300. doi: 10.1046/j.1471-4159.1994.63010291.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received August 31, 1993; revised manuscript received November 8, 1993; accepted November 8, 1993.
- Axonal transport;
- Neurofilament phosphorylation
Abstract: To elucidate the role of neurofilaments in microtubule stabilization in the axon, we studied the effects of β,β′-iminodipropionitrile (IDPN) on the solubility and transport of tubulin as well as neurofilament phosphorylation in the motor fibers of the rat sciatic nerve. IDPN is known to impair the axonal transport of neurofilaments, causing accumulation of neurofilaments in the proximal axon and segregation of neurofilaments to the peripheral axoplasm throughout the nerve. Administration of IDPN at various intervals after radioactive labeling of the spinal cord with l-[35S]methionine revealed that transport inhibition occurred all along the nerve within 1–2 days. Transport of cold-insoluble tubulin, which accounts for 50% of axonal tubulin, was also affected. A significant increase in the proportion of cold-soluble tubulin was observed, reaching a maximum at 3 days after IDPN treatment and returning to the control level in the following weeks. Preceding this change in tubulin solubility, a transient decrease in the phosphorylation level of the 200-kDa neurofilament protein was detected in the ventral root using phosphorylation-dependent antibodies. These early changes agreed in timing with the onset of segregation and transport inhibition, suggesting that interaction between neurofilaments and microtubules possibly regulated by phosphorylation plays a significant role in microtubule stabilization.