title: Cell adhesion molecules regulate Ca2+-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3.
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.
authors.affiliation: Laboratory for Neuronal Growth Mechanisms, Brain Science Institute, The Institute of Physical and Chemical Research, Saitama 351-0198, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ooashi
authors.forename: Akira
authors.initials: A
authors.lastname: Futatsugi
authors.forename: Fumie
authors.initials: F
authors.lastname: Yoshihara
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiguchi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism*; D051379:Mice; D019837:Ryanodine Receptor Calcium Release Channel / Q000145:classification / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D019837:Ryanodine Receptor Calcium Release Channel; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium