State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China.
Dev Cell. 2016 Oct 10;39(1):61-74. doi: 10.1016/j.devcel.2016.09.003. Epub 2016 Sep 29.
For adaptation to complex cellular functions, dynamic cytoskeletal networks are required. There are two major components of the cytoskeleton, microtubules and actin filaments, which form an intricate network maintaining an exquisite cooperation to build the physical basis for their cellular function. However, little is known about the molecular mechanism underlying their synergism. Here, we show that in Caco2 epithelial cells, noncentrosomal microtubules crosstalk with F-actin through their minus ends and contribute to the regulation of focal adhesion size and cell migration. We demonstrate that ACF7, a member of the spectraplakin family of cytoskeletal crosslinking proteins, interacts with Nezha (also called CAMSAP3) at the minus ends of noncentrosomal microtubules and anchors them to actin filaments. Those noncentrosomal microtubules cooperate with actin filaments through retrograde flow to keep their length and orientation perpendicular to the cell edge as well as regulate focal adhesion size and cell migration.
为了适应复杂的细胞功能，需要动态的细胞骨架网络。细胞骨架有两个主要成分，微管和肌动蛋白丝，它们形成一个错综复杂的网络，保持着精细的合作，为其细胞功能建立物理基础。然而，它们协同作用的分子机制知之甚少。在这里，我们表明在 Caco2 上皮细胞中，非中心体微管通过它们的负端与 F-肌动蛋白相互作用，并有助于调节粘着斑的大小和细胞迁移。我们证明，spectraplakin 家族的细胞骨架交联蛋白的一个成员 ACF7，在非中心体微管的负端与 Nezha（也称为 CAMSAP3）相互作用，并将它们锚定在肌动蛋白丝上。这些非中心体微管通过逆行流动与肌动蛋白丝合作，保持它们的长度和方向垂直于细胞边缘，并调节粘着斑的大小和细胞迁移。
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