Alam Samer G, Lovett David, Kim Dae In, Roux Kyle J, Dickinson Richard B, Lele Tanmay P
Department of Chemical Engineering, University of Florida, Bldg. 723, Gainesville, FL 32611, USA.
Sanford Children's Health Research Center, University of South Dakota, Sioux Falls, SD 57104, USA.
J Cell Sci. 2015 May 15;128(10):1901-11. doi: 10.1242/jcs.161703. Epub 2015 Apr 23.
Nuclear positioning is a crucial cell function, but how a migrating cell positions its nucleus is not understood. Using traction-force microscopy, we found that the position of the nucleus in migrating fibroblasts closely coincided with the center point of the traction-force balance, called the point of maximum tension (PMT). Positioning of the nucleus close to the PMT required nucleus-cytoskeleton connections through linker of nucleoskeleton-to-cytoskeleton (LINC) complexes. Although the nucleus briefly lagged behind the PMT following spontaneous detachment of the uropod during migration, the nucleus quickly repositioned to the PMT within a few minutes. Moreover, traction-generating spontaneous protrusions deformed the nearby nucleus surface to pull the nuclear centroid toward the new PMT, and subsequent retraction of these protrusions relaxed the nuclear deformation and restored the nucleus to its original position. We propose that the protruding or retracting cell boundary transmits a force to the surface of the nucleus through the intervening cytoskeletal network connected by the LINC complexes, and that these forces help to position the nucleus centrally and allow the nucleus to efficiently propagate traction forces across the length of the cell during migration.
细胞核定位是一项关键的细胞功能,但迁移细胞如何定位其细胞核尚不清楚。利用牵引力显微镜,我们发现迁移的成纤维细胞中细胞核的位置与牵引力平衡的中心点密切重合,该点称为最大张力点(PMT)。细胞核靠近PMT的定位需要通过核骨架与细胞骨架连接复合体(LINC复合体)实现细胞核与细胞骨架的连接。尽管在迁移过程中尾足自发脱离后细胞核会短暂滞后于PMT,但细胞核会在几分钟内迅速重新定位到PMT。此外,产生牵引力的自发突起使附近的细胞核表面变形,将核质心拉向新的PMT,随后这些突起的回缩减轻了核变形并使细胞核恢复到其原始位置。我们提出,突出或回缩的细胞边界通过由LINC复合体连接的中间细胞骨架网络将力传递到细胞核表面,并且这些力有助于将细胞核定位在中心位置,并使细胞核在迁移过程中能够有效地在细胞长度上传播牵引力。