Calcium-induced synergistic inhibition of a translational factor eEF2 in nerve growth cones
- 作者：Akira Iizuka ; Kumiko Sengoku ; Masumi Iketani ; Fumio Nakamura ; Yasufumi Sato ; Masayuki Matsushita ; Angus C. Nairn ; Ken Takamatsu ; Yoshio Goshima ; Kohtaro Takei
- 关键词：Protein translation ; Growth cone ; Neurite outgrowth ; Calcium ; Elongation factor-2 ; Phosphorylation ; Local protein synthesis ; Calcium influx ; Neural development ; Axon guidance
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：9 February 2007
- 卷：353
- 期：2
- 页码：244-250
- 文件大小：1280 K
摘要
Local protein synthesis in nerve growth cones has been suggested, but how it is controlled remains largely unknown. We found eukaryotic elongation factor-2 (eEF2), a key component of mRNA translation, in growth cones by immunocytochemistry. While phosphorylated eEF2 was weakly distributed in advancing growth cones, eEF2 phosphorylation was increased by high potassium-evoked calcium influx. In the growth cone, calcium elevation increased eEF2 kinase (EF2K), a calcim–calmodulin-dependent enzyme. Calcium also decreased the level of phosphorylated p70-S6 kinase (S6K), a kinase known to inhibit EF2K. Moreover, calcium elevation decreased total eEF2 in growth cones. Since phosphorylated eEF2 inhibits mRNA translation, calcium elevation appears to inhibit mRNA translation in growth cones by a synergistic mechanism involving regulation of EF2K, S6K, and eEF2 itself. Time-lapse imaging showed that calcium elevation induced growth arrest of neurites. The inhibitory effect on mRNA translation may thus be involved in the regulation of neurite outgrowth.