Differential regulation of myosin X movements by its cargos, DCC and neogenin
Differential regulation of myosin X movements by its cargos, DCC and neogenin
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肌球蛋白 X 运动的货物、DCC 和 Neogenin 的差异调节
DOI：
10.1242/jcs.094946
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Xiong, Wen-Cheng
中科院分区：
文献类型：
--
作者：
Liu, Yu;Peng, Yun;Xiong, Wen-Cheng
肌球蛋白X（Myo X），也称为MYO 10，是一种非传统的肌动蛋白为基础的运动蛋白，在丝状伪足的形成中发挥重要作用。它的内丝状伪足运动，与Myo X的功能密切相关的事件，已被广泛研究。然而，Myo X的运动活动及其运动方向是如何调节的，在很大程度上仍然未知。在我们以前的研究中，我们证明了DCC（“在结直肠癌中缺失”）和再生蛋白（再生蛋白1，NEO 1或NGN），一个含有免疫球蛋白结构域的netrins跨膜受体家族，与Myo X相互作用，DCC是Myo X的货物，被递送到培养的神经元的神经突。在这里，我们为DCC和再生蛋白作为Myo X的调节剂提供了证据。DCC促进Myo X沿着基底肌动蛋白丝的运动，并增强Myo-X介导的基底丝状伪足伸长。相比之下，再生蛋白似乎抑制Myo X在基底侧的运动，但增加其向细胞的顶端和背侧的运动，促进背丝状伪足的形成和生长。进一步的研究表明，DCC，而不是再生蛋白，增强整合素介导的酪氨酸磷酸化的粘着斑激酶和基础F-肌动蛋白重组，提供了一个细胞机制，其独特的影响Myo X。因此，这些结果证明了其货物蛋白DCC和再生蛋白对Myo X活性的不同调节作用，揭示了DCC和再生蛋白的不同细胞功能。
Myosin X (Myo X), also known as MYO10, is an unconventional actin-based motor protein that plays an important role in filopodium formation. Its intra-filopodia movement, an event tightly associated with the function of Myo X, has been extensively studied. However, how the motor activity of Myo X and the direction of its movements are regulated remains largely unknown. In our previous study, we demonstrated that DCC (for 'deleted in colorectal carcinoma') and neogenin (neogenin 1, NEO1 or NGN), a family of immunoglobin-domain-containing transmembrane receptors for netrins, interact with Myo X and that DCC is a cargo of Myo X to be delivered to the neurites of cultured neurons. Here, we provide evidence for DCC and neogenin as regulators of Myo X. DCC promotes movement of Myo X along basal actin filaments and enhances Myo-X-mediated basal filopodium elongation. By contrast, neogenin appears to suppress Myo X movement on the basal side, but increases its movement towards the apical and dorsal side of a cell, promoting dorsal filopodium formation and growth. Further studies have demonstrated that DCC, but not neogenin, enhances integrin-mediated tyrosine phosphorylation of focal adhesion kinase and basal F-actin reorganization, providing a cellular mechanism underlying their distinct effects on Myo X. These results thus demonstrate differential regulatory roles on Myo X activity by its cargo proteins, DCC and neogenin, revealing different cellular functions of DCC and neogenin.