Fig. 8.

Cx37 serves as a molecular switch between arrest, proliferation and death in a phosphorylation- and channel-conformation-dependent manner. Our data suggest that the closed state (favored by dephosphorylation at seven high-probability serine residues) of the GJCh and HCh support conformations that arrest cell cycling. Phosphorylation states that support GJChs and HChs that reside predominantly in the lowest conductance state (60-90 pS for GJCh; 100-300 pS for HCh) and briefly transition between this state and larger conductance states are in a conformation that supports proliferation. Phosphorylation states that support significant activity of fully open HChs and GJChs and a low closed state probability induce cell death. Channel conformations in bold denote the preferred GJCh conductance state. Asterisk indicates possible causality.