Impaired synapse function during postnatal development in the absence of CALEB, an EGF-like protein processed by neuronal activity
Impaired synapse function during postnatal development in the absence of CALEB, an EGF-like protein processed by neuronal activity
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DOI：
10.1016/j.neuron.2005.02.027
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发表时间：
2005-04-21
期刊：
影响因子：
16.2
通讯作者：
Rathjen, FG
中科院分区：
文献类型：
--
作者：
Jüttner, R;Moré, MI;Rathjen, FG
为了表征电活动影响突触发育的分子成分，我们寻找受钙流入和谷氨酸受体活性调节的细胞表面蛋白。在这里，我们报告神经元去极化促进了 CALEB 的转化，这导致了具有暴露的 EGF 结构域的截短的跨膜形式。为了表征 CALEB 在突触发育中的作用，研究了 CALEB 缺陷小鼠上丘切片的突触特征。在没有 CALEB 的情况下，突触的数量及其形态特征保持不变。然而，在 CALEB 缺陷小鼠中，突触表现出较高的配对脉冲比、长时间重复激活期间的抑制较少、自发突触后电流率较低，以及在出生后早期但未成熟阶段释放概率较低。我们的研究结果表明 CALEB 为维持早期发育阶段的正常释放概率提供了分子基础。
In an attempt to characterize the molecular components by which electric activity influences the development of synapses, we searched for cell surface proteins modulated by calcium influx and glutamate receptor activity. Here, we report that neuronal depolarization facilitates the conversion of CALEB, which results in a truncated transmembrane form with an exposed EGF domain. To characterize the role of CALEB in synapse development, synaptic features were investigated in slices of the colliculus superior from CALEBdeficient mice. In the absence of CALEB, the number of synapses and their morphological characteristics remained unchanged. However, in CALEB-deficient mice, synapses displayed higher paired-pulse ratios, less depression during prolonged repetitive activation, a lower rate of spontaneous postsynaptic currents, and a lower release probability at early but not mature postnatal stages. Our findings indicate that CALEB provides a molecular basis for maintaining normal release probability at early developmental stages.