Connexins: sensors and regulators of cell cycling

Abstract

It is nowadays well established that gap junctions are critical gatekeepers of cell proliferation, by controlling the intercellular exchange of essential growth regulators. In recent years, however, it has become clear that the picture is not as simple as originally anticipated, as structural precursors of gap junctions can affect cell cycling by performing actions not related to gap junctional intercellular communication. Indeed, connexin hemichannels also foresee a pathway for cell growth communication, albeit between the intracellular compartment and the extracellular environment, while connexin proteins as such can directly or indirectly influence the production of cell cycle regulators independently of their channel activities. Furthermore, a novel set of connexin-like proteins, the pannexins, have lately joined in as regulators of the cell proliferation process, which they can affect as either single units or as channel entities. In the current paper, these multifaceted aspects of connexin-related signalling in cell cycling are reviewed.

Cx26 regulates proliferation of repairing basal airway epithelial cells

“…It is well established that gap junctions contribute to cell homeostasis by allowing the intercellular exchange of essential growth regulators, including ions, nucleotides, sugars, small peptides, RNAs (Kardamia et al, 2007;Vinken et al, 2011), and microRNAs (Lim et al, 2011). Cx26 expression is virtually absent in the normal adult airway epithelium (Chanson, Koval, 2013).…”

Structural Determinants and Proliferative Consequences of Connexin 37 Hemichannel Function in Insulinoma Cells

“…Cx-mediated regulation of cell proliferation can occur by channel-dependent and channel-independent mechanisms (4,25). Previously published data indicated that channel functionality and the C-terminal domain are both necessary for growth suppression by Cx37 (7,9,10).…”

Prognostic value of connexin43 expression in patients with clinically localized prostate cancer

“…[1][2][3] The channels are bicellular structures formed by the members of a family of about 20 related but distinct Cxs. 4,5 Six Cx monomers assemble to form a hemi-gap junction channel or connexon, which, in turn, forms a complete gap junction channel by docking with connexon from an adjacent cell. 2,3 The phosphorylation of connexin43 (Cx43) in its life cycle has been implicated in the regulation of a broad variety of Cx processes, such as the trafficking, assembly/disassembly, degradation, as well as the gating of gap junction channels.…”