Connexin 43 mediated collective cell migration is independent of Golgi orientation

Abstract

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 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.