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

• 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
• ISSN: 0021-9525

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.