Mammalian septins regulate microtubule stability through interaction with the microtubule-binding protein MAPP-1
Mammalian septins regulate microtubule stability through interaction with the microtubule-binding protein MAPP-1
复制标题
DOI：
10.1091/mbc.e05-03-0267
复制
发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Macara, IG
中科院分区：
文献类型：
--
作者：
Kremer, BE;Haystead, T;Macara, IG
哺乳动物败蛋白构成了至少 12 种 GTP 结合蛋白的家族，这些蛋白可以形成异源寡聚物，有时发现与肌动蛋白或微管丝相关。然而，它们的功能尚不清楚。使用 RNA 干扰，我们发现 HeLa 细胞中 septin 表达的抑制导致微管稳定性显着增加。对与 Sept6 共沉淀的蛋白质进行质谱分析，确定微管相关蛋白 MAP4 为 septin 结合伴侣。 MAP4 C 端一半的富含脯氨酸的小区域直接与 Sept 2:6:7 异三聚体和 Sept2 单体结合。三聚体阻断了该 MAP4 片段在体外结合和捆绑微管的能力。在完整细胞中，MAP4 是稳定由隔膜蛋白消耗诱导的微管所必需的。此外，septin 消耗增加了具有异常细胞核的细胞数量，而这种效应被 MAP4 基因沉默所阻断。这些数据确定了哺乳动物细胞中脓毒症的一种新分子功能：通过与 MAP4 相互作用调节微管动力学。
Mammalian septins constitute a family of at least 12 GTP-binding proteins that can form hetero-oligomers and that are sometimes found in association with actin or microtubule filaments. However, their functions are not understood. Using RNA interference, we found that suppression of septin expression in HeLa cells caused a pronounced increase in microtubule stability. Mass spectroscopic analysis of proteins coprecipitating with Sept6 identified the microtubule-associated protein MAP4 as a septin binding partner. A small, proline-rich region in the C-terminal half of MAP4 bound directly to a Sept 2:6:7 heterotrimer, and to the Sept2 monomer. The trimer blocked the ability of this MAP4 fragment to bind and bundle microtubules in vitro. In intact cells, MAP4 was required for the stabilization of microtubules induced by septin depletion. Moreover, septin depletion increased the number of cells with abnormal nuclei, and this effect was blocked by gene silencing of MAP4. These data identify a novel molecular function for septins in mammalian cells: the modulation of microtubule dynamics through interaction with MAP4.