Regulation of neurite growth by spontaneous Ca2+ oscillations in astrocytes
Regulation of neurite growth by spontaneous Ca2+ oscillations in astrocytes
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DOI：
10.1523/jneurosci.2276-07.2007
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发表时间：
2007-08-15
影响因子：
5.3
通讯作者：
Iino, Masamitsu
中科院分区：
文献类型：
--
作者：
Kanemaru, Kazunori;Okubo, Yohei;Iino, Masamitsu
星形胶质细胞在神经突起生长的调节中起着关键作用，但星形胶质细胞中介导这一调节的细胞内信号机制仍不清楚。我们研究了星形胶质细胞内自发的钙振荡与星形胶质细胞介导的神经突起生长的关系。我们产生了钙信号缺乏的星形胶质细胞，在这种细胞中，自发的钙振荡被IP3信号的长期抑制所消除。将海马神经元培养在钙信号缺乏的星形胶质细胞单层上时，树突和轴突的生长受到抑制。轴突生长锥体推进的时间推移成像表明，膜结合分子参与了这种抑制。在六个可能调节神经元生长的候选膜结合分子中，N-钙粘附素在钙信号缺乏的星形胶质细胞中下调。尽管N-钙粘附素的封闭抗体抑制了对照星形胶质细胞的轴突生长，但外源性N-钙粘附素的表达挽救了钙信号缺乏的星形胶质细胞的轴突生长抑制。这些发现表明，自发的钙振荡通过维持星形胶质细胞表面特定的生长促进蛋白的表达来调节星形胶质细胞的功能，促进神经突起的生长，N-钙粘附素就是其中之一。
Astrocytes play a pivotal role in the regulation of neurite growth, but the intracellular signaling mechanism in astrocytes that mediates this regulation remains unclarified. We studied the relationship between spontaneous Ca2+ oscillations in astrocytes and the astrocyte-mediated neurite growth. We generated Ca2+ signal-deficient astrocytes in which spontaneous Ca2+ oscillations were abolished by a chronic inhibition of IP3 signaling. When hippocampal neurons were cultured on a monolayer of Ca2+ signal-deficient astrocytes, the growth of dendrites and axons was inhibited. Time-lapse imaging of the advancement of axonal growth cones indicated the involvement of membrane-bound molecules for this inhibition. Among six candidate membrane-bound molecules that may modulate neuronal growth, N-cadherin was downregulated in Ca2+ signal-deficient astrocytes. Although a blocking antibody to N-cadherin suppressed the axonal growth on control astrocytes, extrinsic N-cadherin expression rescued the suppressed axonal growth on Ca2+ signal-deficient astrocytes. These findings suggest that spontaneous Ca2+ oscillations regulate the astrocytic function to promote neurite growth by maintaining the expression of specific growth-enhancing proteins on their surface, and that N-cadherin is one of such molecules.