Redistribution of connexin 43 during cell division

Abstract

Gap junction channels, once clustered into gap junction plaques, allow communication of essential metabolites between cells. Gap junction plaques have been reported to be lost from the cell surface during cell division. The mechanism involved in this loss of gap junction plaques during mitosis is unclear, but we hypothesize that an endoexocytotic mechanism that results in cytoplasmic double-membraned annular gap junction vesicles is involved. In this study, gap junction plaque changes in dividing cells were examined in SW-13 adrenocortical tumor cells. Endogenous gap junction protein, connexin 43 (Cx43), was detected with immunofluorescence, and live cell imaging was used to monitor green fluorescent protein-tagged Cx43 (Cx43-GFP). Mitotic stages were identified by Hoechst chromosomal staining. During interphase, large gap junction plaques were detected; however, the presence of these plaques decreased, whereas cytoplasmic puncta increased beginning with prophase. The cytoplasmic puncta were demonstrated with immunoelectron microscopy to be Cx43- positive annular gap junction vesicles. As gap junction plaques reformed at cleavage furrows between daughter cells, the number of annular gap junctions decreased during cytokinesis. The data are consistent with the mechanism of gap junction plaque loss during mitosis relying on an endoexocytotic process that results in annular gap junction vesicles formation. The rapid formation of gap junction plaques during cytokinesis points to the intriguing possibility of connexin recycling from annular gap junction vesicles to form gap junction plaques as mitosis is completed.

The E3 ubiquitin ligase NEDD4 induces endocytosis and lysosomal sorting of connexin 43 to promote loss of gap junctions

“…Alternatively, Cx43 might undergo recycling from the multivesicular endosomes to the plasma membrane. In accordance with this model, Cx43 has been shown to be transported to early endosomes during the early phases of mitosis and is thought to undergo recycling to the plasma membrane in the late phases (Boassa et al, 2010;Fykerud et al, 2016;Vanderpuye et al, 2016).…”

Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium

“…We speculate that the interaction between Cx43 junctional complex and tight junction ZO proteins, or with molecules like Par3 that are involved in the PI3K-AKT pathway controlling MSO (Tenvooren et al, 2019), might underlie Cx43mediated MSO. It is unlikely that Cx43 exerts an impact on MSO via its known interaction with tubulin (Sorgen et al, 2018;Vanderpuye et al, 2016), since we rarely observed Cx43 localized near the mitotic spindle (Fig. S6C).…”

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

“…Moreover, connexosomes have been suggested to be able to undergo a transformation into a connexin-enriched multivesicular endosome, which is associated with their fusion with early endosomes [79][80][81][82]. Some studies also indicate that following endocytosis, connexins can under certain conditions undergo recycling from endocytic compartments back to the plasma membrane [32, 75,81,[83][84][85]. It has also been suggested that Cx43 can be transported directly from early secretory compartments to lysosomes without prior transport to the plasma membrane [30].…”