A role for the cytoskeleton-associated protein palladin in neurite outgrowth
A role for the cytoskeleton-associated protein palladin in neurite outgrowth
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DOI：
10.1091/mbc.12.9.2721
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发表时间：
2001-09-01
影响因子：
3.3
通讯作者：
Otey, CA
中科院分区：
文献类型：
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作者：
Boukhelifa, M;Parast, MM;Otey, CA
神经突的生长是神经元成熟的关键步骤，并且已经确定肌动蛋白细胞骨架参与了这一过程。我们实验室的研究人员最近描述了一种名为palladin的新型蛋白质，它已被证明在组织培养的成纤维细胞中的肌动蛋白细胞骨架中发挥重要作用。我们通过蛋白质印迹法研究了palladin在发育中的大鼠脑中的表达，发现E18脑含有palladin的独特变体，其显著小于（类似于85 kDa）在其他发育组织中发现的常见形式（90-92 kDa）。由于组织特异性亚型的表达表明细胞类型特异性功能的可能性，我们研究了palladin在培养的皮层神经元中的定位和功能。Palladin被发现优先针对发展中的轴突，但不是树突，并强烈定位于轴突生长锥。当palladin的表达减弱转染与反义结构在B35神经母细胞瘤细胞系和原代皮层神经元，palladin的表达减少导致神经突生长失败。这些结果暗示palladin作为神经系统发育的重要组成部分，在轴突延伸中具有重要作用。
The outgrowth of neurites is a critical step in neuronal maturation, and it is well established that the actin cytoskeleton is involved in this process. Investigators from our laboratory recently described a novel protein named palladin, which has been shown to play an essential role in organizing the actin cytoskeleton in cultured fibroblasts. We investigated the expression of palladin in the developing rat brain by Western blot and found that the E18 brain contained a unique variant of palladin that is significantly smaller (similar to 85 kDa) than the common form found in other developing tissues (90-92 kDa). Because the expression of a tissue-specific isoform suggests the possibility of a cell type-specific function, we investigated the localization and function of palladin in cultured cortical neurons. Palladin was found preferentially targeted to the developing axon but not the dendrites and was strongly localized to the axonal growth cone. When palladin expression was attenuated by transfection with antisense constructs in both the B35 neuroblastoma cell line and in primary cortical neurons, a reduction in the expression of palladin resulted in a failure of neurite outgrowth. These results implicate palladin as a critical component of the developing nervous system, with an important role in axonal extension.