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- Title
Cell adhesion molecules regulate Ca<sup>2+</sup>-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3.
- Authors
Ooashi, Noriko; Futatsugi, Akira; Yoshihara, Fumie; Mikoshiba, Katsuhiko; Kamiguchi, Hiroyuki
- Abstract
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 Ca2+ 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 Ca2+-induced Ca2+ release (CICR) into the cytosol, leading to attractive turning of the growth cone. In contrast, the growth cone exhibits repulsion when Ca2+ signals are not accompanied by RyR3-mediated CICR. We also propose that the source of Ca2+ influx, rather than its amplitude or the baseline Ca2+ 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.
- Subjects
AXONAL transport; CELL adhesion molecules; DEVELOPMENTAL cytology; CYTOSOL; RYANODINE receptors; CYTOLOGICAL research; PROTEIN kinases
- Publication
Journal of Cell Biology, 2005, Vol 170, Issue 7, p1159
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200503157