REGULATION OF NEURITE OUTGROWTH MEDIATED BY NEURONAL CALCIUM SENSOR-1 AND INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR IN NERVE GROWTH CONES
REGULATION OF NEURITE OUTGROWTH MEDIATED BY NEURONAL CALCIUM SENSOR-1 AND INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR IN NERVE GROWTH CONES
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DOI：
10.1016/j.neuroscience.2009.04.019
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发表时间：
2009-07-07
期刊：
影响因子：
3.3
通讯作者：
Takei, K.
中科院分区：
文献类型：
--
作者：
Iketani, M.;Imaizumi, C.;Takei, K.
钙离子作为细胞内信号通路中重要的第二信使参与多种细胞功能。严格控制的细胞内钙是发育中的神经元的神经突生长所必需的。然而，这一过程的分子机制在很大程度上仍然是未知的。神经元钙传感器-1（NCS-1）是一种高亲和力、低容量的钙结合蛋白，在神经系统中特异性表达。NCS-1分布在整个区域的生长锥位于一个远尖端的神经突起在培养的鸡背根神经节神经元。而在生长锥的中央区域，NCS-1呈簇状分布，并与1型1，4，5-三磷酸肌醇受体（InsP（3）R1）共定位。InsP（3）受体的药理学抑制降低了NCS-1在生长锥中的聚集特异性分布，抑制了神经突的生长，但不改变生长锥的形态。发色团辅助激光灭活（卡利）诱导的生长锥中NCS-1功能的急性和局部丧失导致神经突生长停滞以及板状伪足和丝状伪足退缩。这些发现表明，NCS-1参与了神经突生长和生长锥形态的调节。此外，NCS-1在功能上与InsP 3R 1相连，InsP 3R 1可能在神经突生长的调节中发挥重要作用。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Calcium acts as an important second messenger in the intracellular signal pathways in a variety of cell functions. Strictly controlled intracellular calcium is required for proper neurite outgrowth of developing neurons. However, the molecular mechanisms of this process are still largely unknown. Neuronal calcium sensor-1 (NCS-1) is a high-affinity and low-capacity calcium binding protein, which is specifically expressed in the nervous system. NCS-1 was distributed throughout the entire region of growth cones located at a distal tip of neurite in cultured chick dorsal root ganglion neurons. In the central domain of the growth cone, however, NCS-1 was distributed in a clustered specific pattern and co-localized with the type 1 inositol 1,4,5-trisphosphate receptor (InsP(3)R1). The pharmacological inhibition of InsP(3) receptors decreased the clustered specific distribution of NCS-1 in the growth cones and inhibited neurite outgrowth but did not change the growth cone morphology. The acute and localized loss of NCS-1 function in the growth cone induced by chromophore-assisted laser inactivation (CALI) resulted in the growth arrest of neurites and lamellipodial and filopodial retractions. These findings suggest that NCS-1 is involved in the regulation of both neurite outgrowth and growth cone morphology. In addition, NCS-1 is functionally linked to InsP3R1, which may play an important role in the regulation of neurite outgrowth. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.