LIS1, CLIP-170's key to the dynein/dynactin pathway
LIS1, CLIP-170's key to the dynein/dynactin pathway
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DOI：
10.1128/mcb.22.9.3089-3102.2002
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发表时间：
2002-05-01
影响因子：
5.3
通讯作者：
Reiner, O
中科院分区：
文献类型：
--
作者：
Coquelle, FM;Caspi, M;Reiner, O
CLIP-170是一种正末端跟踪蛋白，可能是一种抗突变因子。已经提出介导动力蛋白/动力肌动蛋白与微管（MT）正末端的缔合，并且它也以动力蛋白/动力蛋白依赖的方式结合到着丝粒，两者都通过其C-末端结构域。该结构域包含两个锌指基序（近端和远端），假设其介导蛋白质-蛋白质相互作用。LIS 1是一种参与脑发育的蛋白质，通过与动力蛋白和其他蛋白质相互作用，在动力蛋白/动力肌动蛋白途径介导的几个过程中起作用。在这里，我们演示了CLIP-170和LIST之间的共定位和直接交互。在哺乳动物细胞中，LIST向着丝粒的募集是动力蛋白/动力蛋白依赖性的，并且CLIP-170在那里的募集依赖于其与位于远端锌指基序中的LIS 1的结合位点。CLIP-170的过表达导致磷酸化LIST同种型和动力蛋白与MT束的锌指依赖性定位，提高了CLIP-170和LIS 1调节动力蛋白/动力蛋白与MT结合的可能性。这项工作表明，LIST是CLIP-170和细胞质动力蛋白之间的调节适配器，在参与货物MT加载和/或MT动力学控制的网站。
CLIP-170 is a plus-end tracking protein which may act as an anticatastrophe factor. It has been proposed to mediate the association of dynein/dynactin to microtubule (MT) plus ends, and it also binds to kinetochores in a dynein/dynactin-dependent fashion, both via its C-terminal domain. This domain contains two zinc finger motifs (proximal and distal), which are hypothesized to mediate protein-protein interactions. LIS1, a protein implicated in brain development, acts in several processes mediated by the dynein/dynactin pathway by interacting with dynein and other proteins. Here we demonstrate colocalization and direct interaction between CLIP-170 and LIST. In mammalian cells, LIST recruitment to kinetochores is dynein/dynactin dependent, and recruitment there of CLIP-170 is dependent on its site of binding to LIS1, located in the distal zinc finger motif. Overexpression of CLIP-170 results in a zinc finger-dependent localization of a phospho-LIST isoform and dynactin to MT bundles, raising the possibility that CLIP-170 and LIS1 regulate dynein/dynactin binding to MTs. This work suggests that LIST is a regulated adapter between CLIP-170 and cytoplasmic dynein at sites involved in cargo-MT loading, and/or in the control of MT dynamics.