Connexin 43 mediated collective cell migration is independent of Golgi orientation

Abstract

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 secretory traffic towards the leading edge by reorienting the Golgi apparatus. However, conflicting results on the positioning of the Golgi relative to the migrating cell raise questions about its regulation. Herein, we address the role of gap junction protein Connexin 43, which connects cells allowing the direct exchange of molecules and also controls the distribution of microtubules. We utilized HeLa WT (wild-type cells lacking Connexin 43) and HeLa 43 cells (stably expressing Connexin 43). We found that functional Connexin 43 channels affected Golgi morphology and reduced the ability of reorientation of Golgi (towards the leading edge) during cell migration. Although Connexin 43 also reduced migration velocity, the front displayed enhanced coherence in movement, implying an augmented collective nature of migration compared to HeLa WT cells lacking the cell-cell connectivity evidenced in HeLa 43. The increase in vimentin and basal actin in HeLa 43 shows that Connexin 43 expression alters the cytoskeleton. Non-invasive measurement of basal membrane height fluctuations revealed that HeLa 43 had a lower membrane tension and a more uniform intra- and inter-cellular distribution than HeLa WT, similar to their coherence in migration. We, therefore, propose that the reduced Golgi reorientation in HeLa 43 might be linked to lesser dependence on directed secretory trafficking, which is believed to be required to buffer the increasing tension caused by migration.