Cell adhesion molecules regulate Ca super(2+)-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3

Axonal growth cones migrate along the correct paths during development, not only directed by guidance cues but also contacted by local environment via cell adhesion molecules (CAMs). Asymmetric Ca super(2+) elevations in the growth cone cytosol induce both attractive and repulsive turning in respons...

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Bibliographic Details
Published in:The Journal of cell biology 2005-09, Vol.170 (7), p.1159-1167
Main Authors: Ooashi, Noriko, Futatsugi, Akira, Yoshihara, Fumie, Mikoshiba, Katsuhiko, Kamiguchi, Hiroyuki
Format: Article
Language:English
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Summary:Axonal growth cones migrate along the correct paths during development, not only directed by guidance cues but also contacted by local environment via cell adhesion molecules (CAMs). Asymmetric Ca super(2+) elevations in the growth cone cytosol induce both attractive and repulsive turning in response to the guidance cues (Zheng, J.Q. 2000. NATURE: 403:89-93; Henley, J.R., K.H. Huang, D. Wang, and M.M. Poo. 2004. NEURON: 44:909-916). Here, we show that CAMs regulate the activity of ryanodine receptor type 3 (RyR3) via cAMP and protein kinase A in dorsal root ganglion neurons. The activated RyR3 mediates Ca super(2+)-induced Ca super(2+) release (CICR) into the cytosol, leading to attractive turning of the growth cone. In contrast, the growth cone exhibits repulsion when Ca super(2+) signals are not accompanied by RyR3-mediated CICR. We also propose that the source of Ca super(2+) influx, rather than its amplitude or the baseline Ca super(2+) level, is the primary determinant of the turning direction. In this way, axon-guiding and CAM-derived signals are integrated by RyR3, which serves as a key regulator of growth cone navigation.
ISSN:0021-9525