Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia 741246, India.
Biol Open. 2023 Oct 15;12(10). doi: 10.1242/bio.060006. Epub 2023 Oct 30.
Cell migration is vital for multiple physiological functions and is involved in the metastatic dissemination of tumour cells in various cancers. For effective directional migration, cells often reorient their Golgi apparatus and, therefore, the secretory traffic towards the leading edge. However, not much is understood about the regulation of Golgi's reorientation. Herein, we address the role of gap junction protein Connexin 43 (Cx43), which connects cells, allowing the direct exchange of molecules. We utilized HeLa WT cells lacking Cx43 and HeLa 43 cells, stably expressing Cx43, and found that functional Cx43 channels affected Golgi morphology and reduced the reorientation of Golgi during cell migration. Although the migration velocity of the front was reduced in HeLa 43, the front displayed enhanced coherence in movement, implying an augmented collective nature of migration. On BFA treatment, Golgi was dispersed and the high heterogeneity in inter-regional front velocity of HeLa WT cells was reduced to resemble the HeLa 43. HeLa 43 had higher vimentin expression and stronger basal F-actin. Furthermore, non-invasive measurement of basal membrane height fluctuations revealed a lower membrane tension. We, therefore, propose that reorientation of Golgi is not the major determinant of migration in the presence of Cx43, which induces collective-like coherent migration in cells.
细胞迁移对于多种生理功能至关重要,并且参与了各种癌症中肿瘤细胞的转移扩散。为了实现有效的定向迁移,细胞通常会重新定向它们的高尔基体,并因此将分泌物流朝向前沿。然而,关于高尔基体的重新定向的调节机制,我们知之甚少。在此,我们研究了间隙连接蛋白 Connexin 43(Cx43)的作用,该蛋白连接细胞,允许分子直接交换。我们利用缺乏 Cx43 的 HeLa WT 细胞和稳定表达 Cx43 的 HeLa 43 细胞,发现功能性 Cx43 通道会影响高尔基体的形态,并减少细胞迁移过程中高尔基体的重新定向。尽管 HeLa 43 细胞的前沿迁移速度降低,但前沿显示出运动的增强一致性,表明迁移的集体性质增强。在用 BFA 处理后,高尔基体被分散,HeLa WT 细胞中区域间前沿速度的高度异质性降低,类似于 HeLa 43 细胞。HeLa 43 细胞中波形蛋白的表达更高,基底 F-肌动蛋白更强。此外,基底膜高度波动的非侵入性测量显示出更低的膜张力。因此,我们提出,在存在 Cx43 的情况下,高尔基体的重新定向不是迁移的主要决定因素,而是诱导细胞中类似集体的一致迁移。