CAMSAP1 breaks the homeostatic microtubule network to instruct neuronal polarity
CAMSAP1 breaks the homeostatic microtubule network to instruct neuronal polarity
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CAMSAP1 打破稳态微管网络来指示神经元极性
DOI：
10.1073/pnas.1913177117
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Meng Wenxiang
中科院分区：
文献类型：
--
作者：
Zhou Zhengrong;Xu Honglin;Li Yuejia;Yang Mengge;Zhang Rui;Shiraishi Aki;Kiyonari Hiroshi;Liang Xin;Huang Xiahe;Wang Yingchun;Xie Qi;Liu Shuai;Chen Rongqing;Bao Lan;Guo Weixiang;Wang Yu;Meng Wenxiang
轴突/树突的正确形成对于神经元实现其功能至关重要，而微管是这一过程的最终执行者。然而，极化信号如何传递到微管来指导轴突/树突分化仍然是未知的。在这里，我们发现，CAMSAP 1，微管负端结合蛋白，驱动神经元极化，迁移和皮层分层。我们还证明了CAMSAP 1的微管结合能力对于保护微管负端和保存微管再生的“种子”至关重要，并且这种能力受MARK 2调节。因此，我们的研究结果表明，CAMSAP 1通过触发微管在神经元过程中的不平衡分布来控制神经元极化; CAMSAP家族成员通过改变微管的数量和质量来调节轴突形成。轴突/树突极性的建立是神经元整合到功能回路中的基础，而这一过程严重依赖于微管（MT）。在建立过程的早期阶段，轴突中的MT随着神经元的形态学构建而发生显著变化;然而，MT网络的变化是如何触发的尚不清楚。在这里，我们表明，CAMSAP 1起着决定性的作用，在神经元轴突的识别过程中，通过调节MT的数量。缺乏CAMSAP 1的神经元在体外形成多轴突表型，而多极-双极转换和径向迁移在体内被阻断。我们证明了极性调节剂MARK 2激酶磷酸化CAMSAP 1并影响其与MT结合的能力，这反过来又改变了MT负端的保护，并引发了MT的不对称分布。我们的研究结果表明，极化MT网络在神经元中是一个决定性因素，在建立轴突/树突极性，最初是由极化信号触发。
Significance Proper formation of axon/dendrites is critical for the neuron to fulfill its function, and microtubules are the final performer in this process. However, how polarizing signals transduce to microtubules to instruct axon/dendrite differentiation remains unknown. Here we found that CAMSAP1, a microtubule minus-end binding protein, drives neuronal polarization, migration, and cortical lamination. We also demonstrate that the microtubule-binding ability of CAMSAP1 is critical for the protection of microtubule minus-ends and preservation of the “seeds” for microtubule regeneration, and this ability is regulated by MARK2. Thus, our findings reveal that CAMSAP1 controls neuronal polarization via triggering an unbalanced distribution of microtubules among neuronal processes; CAMSAP family members regulate axon formation by changing the quantity and quality of microtubules. The establishment of axon/dendrite polarity is fundamental for neurons to integrate into functional circuits, and this process is critically dependent on microtubules (MTs). In the early stages of the establishment process, MTs in axons change dramatically with the morphological building of neurons; however, how the MT network changes are triggered is unclear. Here we show that CAMSAP1 plays a decisive role in the neuronal axon identification process by regulating the number of MTs. Neurons lacking CAMSAP1 form a multiple axon phenotype in vitro, while the multipolar-bipolar transition and radial migration are blocked in vivo. We demonstrate that the polarity regulator MARK2 kinase phosphorylates CAMSAP1 and affects its ability to bind to MTs, which in turn changes the protection of MT minus-ends and also triggers asymmetric distribution of MTs. Our results indicate that the polarized MT network in neurons is a decisive factor in establishing axon/dendritic polarity and is initially triggered by polarized signals.
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DOI：
10.1523/jneurosci.14-05-02818.1994
发表时间：
1994-05
期刊：
--
影响因子：
--
作者：
Wenqian Yu;P. Baas
通讯作者：
Wenqian Yu;P. Baas
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
Rui Zhu;Kazuhiro Fukui;Jing-Hao Xue
通讯作者：
Rui Zhu;Kazuhiro Fukui;Jing-Hao Xue
影响因子：
3
作者：
Shelly, Maya;Poo, Mu-Ming
通讯作者：
Poo, Mu-Ming
DOI：
10.1073/pnas.1404133111
发表时间：
2014-04-22
影响因子：
11.1
作者：
Hendershott, Melissa C.;Vale, Ronald D.
通讯作者：
Vale, Ronald D.
影响因子：
7.7
作者：
Yan Wang;Menglong Rui;Quan Tang;Shufeng Bu;F. Yu
通讯作者：
Yan Wang;Menglong Rui;Quan Tang;Shufeng Bu;F. Yu