Clathrin assembly protein AP180 and CALM differentially control axogenesis and dendrite outgrowth in embryonic hippocampal neurons.
Clathrin assembly protein AP180 and CALM differentially control axogenesis and dendrite outgrowth in embryonic hippocampal neurons.
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DOI：
10.1523/jneurosci.2471-08.2008
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发表时间：
2008-10-08
期刊：
影响因子：
--
通讯作者：
Yao PJ
中科院分区：
文献类型：
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作者：
Bushlin I;Petralia RS;Wu F;Harel A;Mughal MR;Mattson MP;Yao PJ
新数据表明，与上皮细胞非常相似，神经元的极化生长需要分泌途径和内吞途径。已知网格蛋白组装蛋白 AP180 和 CALM 参与网格蛋白介导的内吞作用，但它们在哺乳动物神经元中的作用，特别是在突触发生之前的发育过程中的作用尚不清楚。在这里，我们提供的证据表明 AP180 和 CALM 在建立极性和控制胚胎海马神经元轴突和树突的生长方面发挥着关键作用。 AP180 的敲低主要损害轴突发育，而降低 CALM 水平会导致树突营养不良。相反，过度表达 AP180 或 CALM 的神经元会产生多个轴突。超微结构分析表明，与 AP180 相比，CALM 与更广泛的细胞内运输细胞器相关。功能分析表明，AP180 缺陷和 CALM 缺陷神经元的内吞作用均减少。此外，缺乏 CALM 的神经元表现出分泌运输中断。我们的数据证明了 AP180 和 CALM 在细胞内运输中以前未知的功能，这对神经元的生长至关重要。
Emerging data suggest that, much like epithelial cells, the polarized growth of neurons requires both the secretory and endocytic pathways. The clathrin assembly proteins AP180 and CALM are known to be involved in clathrin-mediated endocytosis, but their roles in mammalian neurons, and, in particular, in developmental processes prior to synaptogenesis, are unknown. Here we provide evidence that AP180 and CALM play critical roles in establishing the polarity and controlling the growth of axons and dendrites in embryonic hippocampal neurons. Knockdown of AP180 primarily impairs axonal development, while reducing CALM levels results in dendritic dystrophy. Conversely, neurons that overexpress AP180 or CALM generate multiple axons. Ultrastructural analysis shows that CALM affiliates with wider range of intracellular trafficking organelles than does AP180. Functional analysis shows that endocytosis is reduced in both AP180-deficient and CALM-deficient neurons. Additionally, CALM-deficient neurons show disrupted secretory transport. Our data demonstrate previously unknown functions for AP180 and CALM in intracellular trafficking that is essential in the growth of neurons.