Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts.
Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts.
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DOI：
10.1091/mbc.e13-06-0307
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发表时间：
2013-12
影响因子：
3.3
通讯作者：
Gundersen GG
中科院分区：
文献类型：
--
作者：
Chang W;Folker ES;Worman HJ;Gundersen GG
Emerin（一种核膜蛋白）和肌球蛋白IIB通过调节核运动的方向性和背侧肌动蛋白索流动来促进核运动。Emerin与肌球蛋白IIB相互作用，并且是其核周定位所必需的。结果表明，核膜积极组织细胞质极性。在迁移的成纤维细胞中，核的向后移动使中心体朝向前缘。核运动的结果耦合向后移动，背侧肌动蛋白电缆的细胞核的nesprin-2G和SUN 2的线性阵列，称为跨膜肌动蛋白相关的核（TAN）线。A型核纤层蛋白锚定TAN线，促使我们测试Emerin（一种与核纤层蛋白和TAN线蛋白相互作用的核膜蛋白）是否有助于核运动。在成纤维细胞耗尽的Emerin，核无方向移动或完全无法移动。与这些核运动缺陷一致，背侧肌动蛋白电缆流是无方向性的细胞缺乏emerin。TAN线形成正常的细胞缺乏emerin和协调不稳定的核运动，虽然在20%的情况下，TAN线滑过不动的核。肌球蛋白II驱动肌动蛋白流动，而肌球蛋白IIB的耗竭，但不是肌球蛋白IIA，表现出类似的非定向核运动和肌动蛋白流动在emerin耗竭细胞。肌球蛋白IIB特异性与emerin共免疫沉淀，emerin耗竭阻止肌球蛋白IIB定位在细胞核附近。这些结果表明，emerin功能与肌球蛋白IIB的肌动蛋白流动和核运动成纤维细胞，这表明一个新的功能，为核膜组织方向肌动蛋白流动和细胞质极性。
Emerin, a nuclear membrane protein, and myosin IIB contribute to nuclear movement by regulating the directionality of nuclear movement and dorsal actin cable flow. Emerin interacts with myosin IIB and is required for its perinuclear localization. The results show that the nuclear envelope actively organizes cytoplasmic polarity. In migrating fibroblasts, rearward movement of the nucleus orients the centrosome toward the leading edge. Nuclear movement results from coupling rearward-moving, dorsal actin cables to the nucleus by linear arrays of nesprin-2G and SUN2, termed transmembrane actin-associated nuclear (TAN) lines. A-type lamins anchor TAN lines, prompting us to test whether emerin, a nuclear membrane protein that interacts with lamins and TAN line proteins, contributes to nuclear movement. In fibroblasts depleted of emerin, nuclei moved nondirectionally or completely failed to move. Consistent with these nuclear movement defects, dorsal actin cable flow was nondirectional in cells lacking emerin. TAN lines formed normally in cells lacking emerin and were coordinated with the erratic nuclear movements, although in 20% of the cases, TAN lines slipped over immobile nuclei. Myosin II drives actin flow, and depletion of myosin IIB, but not myosin IIA, showed similar nondirectional nuclear movement and actin flow as in emerin-depleted cells. Myosin IIB specifically coimmunoprecipitated with emerin, and emerin depletion prevented myosin IIB localization near nuclei. These results show that emerin functions with myosin IIB to polarize actin flow and nuclear movement in fibroblasts, suggesting a novel function for the nuclear envelope in organizing directional actin flow and cytoplasmic polarity.