Microtubule-associated type II protein kinase A is important for neurite elongation.
Microtubule-associated type II protein kinase A is important for neurite elongation.
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DOI：
10.1371/journal.pone.0073890
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hwang E
中科院分区：
文献类型：
--
作者：
Huang YA;Kao JW;Tseng DT;Chen WS;Chiang MH;Hwang E
神经发生是神经元产生广泛的轴突和树突的过程。微管细胞骨架在神经生成过程中起着至关重要的作用。我们之前的研究表明，微管上II型蛋白激酶A （PKA）的数量在神经元分化和神经细胞发生过程中显著增加。虽然PKA的整体池已被证明参与各种神经元过程，但微管相关PKA在神经发生过程中的功能仍在很大程度上未知。首先，我们发现PKA定位于不同神经元的微管区。由于PKA对多种细胞功能至关重要，因此全面抑制PKA活性将导致神经元中各种各样的表型。为了在不改变PKA总水平的情况下检测微管相关PKA的功能，我们利用了神经元特异性PKA锚定蛋白MAP2。过度表达与II型PKA结合但不能与游离海马神经元的微管细胞骨架结合的显性负MAP2结构将PKA从微管中移除，导致神经突伸长受损。此外，我们证明PKA与微管的关联也可以增强非神经元P19细胞的细胞突出。过度表达不将PKA定位于微管细胞骨架的MAP2缺失构建体，导致非神经元细胞比过度表达将PKA锚定在微管上的野生型MAP2的对照细胞产生更短的细胞突起。最后，我们证明了微管相关的PKA促进突起伸长的能力与MAP2磷酸化无关。这表明靠近微管细胞骨架的其他蛋白质参与了这一过程。
Neuritogenesis is a process through which neurons generate their widespread axon and dendrites. The microtubule cytoskeleton plays crucial roles throughout neuritogenesis. Our previous study indicated that the amount of type II protein kinase A (PKA) on microtubules significantly increased upon neuronal differentiation and neuritogenesis. While the overall pool of PKA has been shown to participate in various neuronal processes, the function of microtubule-associated PKA during neuritogenesis remains largely unknown. First, we showed that PKA localized to microtubule-based region in different neurons. Since PKA is essential for various cellular functions, globally inhibiting PKA activity will causes a wide variety of phenotypes in neurons. To examine the function of microtubule-associated PKA without changing the total PKA level, we utilized the neuron-specific PKA anchoring protein MAP2. Overexpressing the dominant negative MAP2 construct that binds to type II PKA but cannot bind to the microtubule cytoskeleton in dissociated hippocampal neurons removed PKA from microtubules and resulted in compromised neurite elongation. In addition, we demonstrated that the association of PKA with microtubules can also enhance cell protrusion using the non-neuronal P19 cells. Overexpressing a MAP2 deletion construct which does not target PKA to the microtubule cytoskeleton caused non-neuronal cells to generate shorter cell protrusions than control cells overexpressing wild-type MAP2 that anchors PKA to microtubules. Finally, we demonstrated that the ability of microtubule-associated PKA to promote protrusion elongation was independent of MAP2 phosphorylation. This suggests other proteins in close proximity to the microtubule cytoskeleton are involved in this process.
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发表时间：
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影响因子：
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作者：
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