Examination of the regulation of gap junction communication and connexin 43 phosphorylation during the cell cycle.

摘要

Gap junction communication (GJC) can act as a tumor suppressor. Loss of the ability to engage in GJC is an early, epigenetic event in tumorigenisis. This study examines the regulation of GJC and connexin43 phosphorylation during the cell cycle. The ability to assemble junctions and Cx43 phosphorylation are inversely related during the cell cycle. Phosphorylation on S368 and phosphorylation, in general, increase as cells progress through the cell cycle while gap junction assembly decreases. These data suggest a model where cells with high proliferative potential lose the ability to assemble gap junctions. This may represent a mechanism by which potential tumor cells initially lose the ability to engage in gap junction communication becoming isolated from gap junction mediated growth control. Furthermore, there appear to be different communication compartments within and between quiescent and proliferative cells. S phase cells are capable of extensive dye transfer with other S phase cells and are able to receive dye from G0 cells. G0 or quiescent cells, on the other hand, are not as extensively coupled nor are they able to receive dye from S phase cells. Thus, it appears that cells in different stages of the cell cycle can modulate the extent to which molecules are shared. In addition, asymmetry in dye transfer can occur via differences in cells, rather than the specific connexins expressed. It appears that differences in the phosphorylation state of connexins in these different cell stages may be able to modulate the behavior of the gap junction channel. Thus, gap junction communication and connexin43 phosphorylation do appear to be regulated at many levels during the cell cycle.