UNC-45A is required for neurite extension via controlling NMII activation
UNC-45A is required for neurite extension via controlling NMII activation
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DOI：
10.1091/mbc.e16-06-0381
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发表时间：
2017-05-15
影响因子：
3.3
通讯作者：
Bazzaro, Martina
中科院分区：
文献类型：
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作者：
Iizuka, Yoshie;Mooneyham, Ashley;Bazzaro, Martina
UNC-45A 是 UNC-45/CRO1/She4p 蛋白家族的高度保守成员，充当常规和非常规肌球蛋白的伴侣。 NMII 介导收缩性和基于肌动蛋白的运动，这是适当的生长锥运动和神经突延伸的基础。 UNC-45A 在神经元分化中的存在和作用在很大程度上尚不清楚。在这里，我们证明 UNC-45A 是调节生长锥动力学的多蛋白复合物中一种新颖的生长锥定位、NMII 相关成分。我们证明 UNC-45A 对于神经元存活来说是可有可无的，但对于神经突伸长是必需的。从机制上讲，UNC-45A 的丢失会导致 NMII 激活水平增加。总的来说，我们的结果为神经突生长的分子机制提供了新的见解，并将 UNC-45A 定义为神经元中 NMII 介导的细胞过程的新型主要调节剂。
UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins, which act as chaperones for conventional and nonconventional myosins. NMII mediates contractility and actin-based motility, which are fundamental for proper growth cone motility and neurite extension. The presence and role of UNC-45A in neuronal differentiation have been largely unknown. Here we demonstrate that UNC-45A is a novel growth cone-localized, NMII-associated component of the multiprotein complex regulating growth cone dynamics. We show that UNC-45A is dispensable for neuron survival but required for neurite elongation. Mechanistically, loss of UNC-45A results in increased levels of NMII activation. Collectively our results provide novel insights into the molecular mechanisms of neurite growth and define UNC-45A as a novel and master regulator of NMII-mediated cellular processes in neurons.