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Neurosci Res. 2012 Aug;73(4):269-74. doi: 10.1016/j.neures.2012.05.010. Epub 2012 Jun 7.

Intracellular signaling and membrane trafficking control bidirectional growth cone guidance.

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  • 1Laboratory for Neuronal Growth Mechanisms, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.


The formation of precise neuronal networks is critically dependent on the motility of axonal growth cones. Extracellular gradients of guidance cues evoke localized Ca(2+) elevations to attract or repel the growth cone. Recent studies strongly suggest that the polarity of growth cone guidance, with respect to the localization of Ca(2+) signals, is determined by Ca(2+) release from the endoplasmic reticulum (ER) in the following manner: Ca(2+) signals containing ER Ca(2+) release cause growth cone attraction, while Ca(2+) signals without ER Ca(2+) release cause growth cone repulsion. Recent studies have also shown that exocytic and endocytic membrane trafficking can drive growth cone attraction and repulsion, respectively, downstream of Ca(2+) signals. Most likely, these two mechanisms underlie cue-induced axon guidance, in which a localized imbalance between exocytosis and endocytosis dictates bidirectional growth cone steering. In this Update Article, I summarize recent advances in growth cone research and propose that polarized membrane trafficking plays an instructive role to spatially localize steering machineries, such as cytoskeletal components and adhesion molecules.

Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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