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First published online 27 March 2007
doi: 10.1242/jcs.001461
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Research Article |
1 Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan
2 Laboratory of Metabolic Regulation Research, Kyushu University Bio-Architecture Center, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan
3 Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama 240-8501, Japan
4 CREST, JST, 4-1-8 Honcho, Kawaguchi 332-0012, Japan
* Author for correspondence (e-mail: kaoru{at}mitils.jp)
Accepted 26 February 2007
The regulation of microtubule dynamics is important for the appropriate arborization of neuronal dendrites during development, which in turn is critical for the formation of functional neural networks. Here we show that stathmin, a microtubule destabilizing factor, is downregulated at both the expression and activity levels during cerebellar development, and this down-regulation contributes to dendritic arborization. Stathmin overexpression drastically limited the dendritic growth of cultured Purkinje cells. The stathmin activity was suppressed by neural activity and CaMKII-dependent phosphorylation at Ser16, which led to dendritic arborization. Stathmin phosphorylation at Ser16 was mediated by the activation of voltage-gated calcium channels and metabotropic glutamate receptor 1. Although overexpression of SCG10, a member of the stathmin family, also limited the dendritic arborization, SCG10 did not mediate the CaMKII regulation of dendritic development. These results suggest that calcium elevation activates CaMKII, which in turn phosphorylates stathmin at Ser16 to stabilize dendritic microtubules. siRNA knockdown of endogenous stathmin significantly reduced dendritic growth in Purkinje cells. Thus, these data suggest that proper regulation of stathmin activity is a key factor for controlling the dendritic microtubule dynamics that are important for neuronal development.
Key words: Calcium signal, Dendritic arborization, Development, Microtubule dynamics, Phosphorylation, Stathmin
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