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Previous Article | Next Article
Volume 16, Number 10, Issue of May 15, 1996 pp. 3236-3246
Copyright ©1996 Society for NeuroscienceMicrotubule Stability Decreases Axon Elongation but Not Axoplasm Production
Received Nov. 1, 1995; revised Feb. 21, 1996; accepted Feb. 26, 1996.
M. William Rochlin1, Karen M. Wickline2, and Paul C. Bridgman1 1 Department of Anatomy and Neurobiology, Washington University School of Medicine, and 2 Department of Pediatrics, St. Louis Children's Hospital, St. Louis, Missouri 63110
Microtubules are a primary cytoskeletal constituent of axons and growth cones. In addition to serving as a scaffolding for axon assembly, they also provide a means of transport of organelles that are essential for outgrowth and maintenance of synaptic function. Pharmacological manipulations that disrupt net assembly of microtubules also interfere with growth cone advance and axon extension. Less is known about the effects of disrupting microtubule dynamics without affecting net assembly. To investigate this, we studied the effects of low doses of nocodazole on axon extension and microtubule organization in rat superior cervical ganglion neurons. We report that 165-330 nM nocodazole significantly reduces axon extension rate and increases axon diameter without affecting the rate of production of axoplasm or microtubule polymer, and without decreasing the average length or number of microtubules. Two observations suggested that microtubule dynamics were depressed by this dose of nocodazole. First, this treatment eliminated the highly divergent lengths and positions of microtubules characteristic of normal growth cones, inducing an array in which each microtubule terminated at roughly the same position in the proximal regions of the growth cone. Second, there was a decrease in the proportion of microtubule length containing mostly tyrosinated (newly assembled)
-tubulin and an increase in the proportion of microtubule length containing mostly acetylated (older, more stable)
Key words: microtubule; axon; polymerization; nocodazole; dynamic instability; growth cone
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