PTTG1/securin modulates microtubule nucleation and cell migration.
PTTG1/securin modulates microtubule nucleation and cell migration.
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DOI：
10.1091/mbc.e10-10-0838
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发表时间：
2011-11
影响因子：
3.3
通讯作者：
Pintor-Toro JA
中科院分区：
文献类型：
--
作者：
Moreno-Mateos MA;Espina ÁG;Torres B;Gámez del Estal MM;Romero-Franco A;Ríos RM;Pintor-Toro JA
PTTG 1与高尔基体和中心体的顺式面相关，与参与微管成核的蛋白质形成复合物。PTTG 1缺失导致中心体和非中心体微管成核延迟，并导致细胞极化和迁移缺陷。垂体瘤转化基因1（PTTG 1），也称为securin，已经涉及许多生物学功能，包括抑制姐妹染色单体分离、DNA修复、器官发育以及调节血管生成和转移因子的表达和分泌。尽管securin的这些功能中的大多数似乎依赖于PTTG 1在细胞核中的定位，但在细胞质中也检测到一部分蛋白质。在这里，我们证明，在不同的细胞类型，一部分的细胞质PTTG 1与高尔基体的顺式面对，这种定位依赖于PTTG 1磷酸化状态。在这个细胞器中，PTTG 1与参与微管成核的蛋白质（包括GM 130、AKAP 450和γ-微管蛋白）形成复合物。RNA干扰介导的PTTG 1耗竭导致中心体和非中心体微管成核延迟。缺乏PTTG 1的细胞在伤口愈合试验中显示出细胞极化和迁移的严重缺陷。据我们所知，这是第一个研究报告的作用，PTTG 1在微管成核和细胞极化，两个过程直接参与细胞迁移。我们相信这些发现将有助于理解PTTG 1介导的生物学功能的机制。
PTTG1 is associated with the cis face of the Golgi apparatus and the centrosome, forming a complex with proteins involved in microtubule nucleation. PTTG1 depletion produces a delay in centrosomal and noncentrosomal microtubule nucleation and causes defects in both cell polarization and migration. Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm. Here we demonstrate that, in different cell types, a portion of cytoplasmic PTTG1 is associated with the cis face of the Golgi apparatus and that this localization depends on PTTG1 phosphorylation status. In this organelle, PTTG1 forms a complex with proteins involved in microtubule nucleation, including GM130, AKAP450, and γ-tubulin. RNA interference–mediated depletion of PTTG1 produces a delay in centrosomal and noncentrosomal microtubule nucleation. Cells lacking PTTG1 show severe defects in both cell polarization and migration in wound-healing assays. To our knowledge, this is the first study reporting the role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration. We believe that these findings will contribute to understanding the mechanisms underlying PTTG1-mediated biological functions.