Effects of melatonin on microtubule assembly depend on hormone concentration: Role of melatonin as a calmodulin antagonist
Article first published online: 30 JAN 2007
Journal of Pineal Research
Volume 17, Issue 2, pages 55–62, September 1994
How to Cite
Huerto-Delgadillo, L., Antón-Tay, F. and Benitez-King, G. (1994), Effects of melatonin on microtubule assembly depend on hormone concentration: Role of melatonin as a calmodulin antagonist. Journal of Pineal Research, 17: 55–62. doi: 10.1111/j.1600-079X.1994.tb00114.x
- Issue published online: 30 JAN 2007
- Article first published online: 30 JAN 2007
- Received March 8, 1994.; accepted May 4, 1994.
- mechanism of action;
- N1E-115 cells;
- calmodulin antagonists
Huerto-Delgadillo L, Antón-Tay F, Benítez-King G. Effects of melatonin on microtubule assembly depend on hormone concentration: rate of melatonin as a calmodulin antagonist. J. Pineal Res. 1994: 17: 55–62. ©Munksgaard, 1994
Melatonin may play a key role in cytoskeletal rearrangements through its calmodulin antagonism. In the present work, we tested this hypothesis by studying melatonin effects on both microtubule polymerization in vitro and cytoskeletons in situ. Microtubule assembly is a dynamic process inhibited by Ca2+/calmodulin. Calmodulin antagonists prevent the inhibition by binding to Ca2+-activated calmodulin, thus causing microtubule enlargement. In the presence of calmodulin (5 μM) and CaCl2 (1 mM), polymerization at equilibrium was inhibited by 40%. Complete reversal of the Ca2+/calmodulin effect on microtubules was observed with 10-9 M melatonin or with 10-5 M trifluoperazine or 1 μg/ml of compound 48/80. In the absence of Ca2+/calmodulin, melatonin at 10-5 M inhibited tubulin polymerization like 10-4 M trifluoperazine does. Melatonin effects on microtubule assembly at both nanomolar and micromolar ranges were corroborated in cytoskeletons in situ. Therefore, it is suggested that at a low concentration (10-9 M), cytoskeletal melatonin effects are mediated by its antagonism to Ca2+/calmodulin. At a higher concentration (10-5 M), non-specific binding of melatonin to tubulin occurs, thus overcoming the melatonin antgonism to Ca2+/calmodulin. The results support the hypothesis that under physiological conditions, melatonin synchronizes different body rhythms through cytoskeletal rearrangements mediated by its calmodulin antagonism.