Microtubule stabilization by Mdp3 is partially attributed to its modulation of HDAC6 in addition to its association with tubulin and microtubules.
Microtubule stabilization by Mdp3 is partially attributed to its modulation of HDAC6 in addition to its association with tubulin and microtubules.
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Mdp3 的微管稳定性部分归因于其对 HDAC6 的调节以及与微管蛋白和微管的关联
DOI：
10.1371/journal.pone.0090932
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Tala;Sun X;Chen J;Zhang L;Liu N;Zhou J;Li D;Liu M
微管介导的细胞事件，如细胞内运输和细胞极性的维持，高度依赖于微管稳定性，而微管稳定性是由细胞中一系列微管相关蛋白（MAPs）控制的。MAP7结构域蛋白3 （Mdp3）最近被确定为微管稳定性的关键调节因子。然而，Mdp3是如何实现这一功能的仍然是一个谜。在这项研究中，通过检查微管蛋白在聚合物和可溶性二聚体形式之间的分配，我们发现Mdp3可以保护微管免受冷或诺可达唑诱导的解聚。免疫印迹和免疫荧光显微镜显示，敲低Mdp3表达可显著降低微管蛋白乙酰化水平。体外微管蛋白聚合实验表明，Mdp3的氨基末端区域对其稳定微管的能力是必要的。免疫沉淀和拉下实验表明，除了与微管蛋白和微管相关外，氨基末端区域介导了Mdp3与组蛋白去乙酰化酶6 （HDAC6）的相互作用。免疫荧光显微镜进一步证实内源性Mdp3和HDAC6共定位于细胞质中。此外，Mdp3的缺失显著增加了HDAC6对微管蛋白去乙酰化的活性。这些发现表明，Mdp3通过与微管蛋白和微管的结合以及调控HDAC6活性来控制微管的稳定性。
Microtubule-mediated cellular events such as intracellular transport and the maintenance of cell polarity are highly dependent upon microtubule stability, which is controlled by a repertoire of microtubule-associated proteins (MAPs) in the cell. MAP7 domain-containing protein 3 (Mdp3) has recently been identified as a critical regulator of microtubule stability. However, it remains elusive how Mdp3 carries out this function. In this study, by examination of tubulin partitioning between the polymer and soluble dimer forms, we found that Mdp3 could protect microtubules from cold- or nocodazole-induced depolymerization. Immunoblotting and immunofluorescence microscopy showed that knockdown of Mdp3 expression significantly reduced the level of tubulin acetylation. In vitro tubulin polymerization assays revealed that the amino-terminal region of Mdp3 was necessary for its ability to stabilize microtubules. Immunoprecipitation and pulldown experiments showed that the amino-terminal region mediated the interaction of Mdp3 with histone deacetylase 6 (HDAC6), in addition to its association with tubulin and microtubules. Immunofluorescence microscopy further demonstrated that endogenous Mdp3 and HDAC6 colocalized in the cytoplasm. Moreover, depletion of Mdp3 dramatically increased the activity of HDAC6 toward tubulin deacetylation. These findings suggest that Mdp3 controls microtubule stability through its binding to tubulin and microtubules as well as its regulation of HDAC6 activity.
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影响因子：
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作者：
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64.8
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