Cell adhesion molecules regulate Ca2+-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3.
Cell adhesion molecules regulate Ca2+-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3.
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DOI：
10.1083/jcb.200503157
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发表时间：
2005-09-26
期刊：
影响因子：
--
通讯作者：
Kamiguchi H
中科院分区：
文献类型：
--
作者：
Ooashi N;Futatsugi A;Yoshihara F;Mikoshiba K;Kamiguchi H
轴突生长锥在发育过程中沿着正确的路径迁移，不仅由引导信号引导，还通过细胞黏附分子(CAM)与局部环境接触。生长锥细胞质中不对称的钙离子升高会引起吸引和排斥的转向，以响应引导线索(郑，J.Q.2000)。大自然。403：89-93；Henley，J.R.，K.H.Huang，D.Wang和M.M.Poo。2004年。神经元。44：909-916)。在这里，我们表明，CAMS通过cAMP和蛋白激酶A调节背根神经节神经元中兰尼定受体3(RyR3)的活性。激活的RyR3介导钙离子诱导的钙离子释放(CICR)进入胞浆，导致生长锥发生吸引人的转向。相反，当Ca~(2+)信号不伴随RyR3介导的CICR时，生长锥表现出排斥。我们还认为，钙离子内流的来源，而不是其幅度或基线钙离子水平，是决定转向的主要因素。通过这种方式，轴突引导和CAM衍生的信号由RyR3整合，RyR3作为生长锥体导航的关键调节因子。
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.
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