The Lampe laboratory investigates the kinases and pathways that regulate gap junction function during development, epidermal wounding, cardiac ischemia and cancinogenesis. Gap junctions allow diffusion of small molecules (<1000 MW) between adjacent cells via matched cell-to-cell membrane channels. Cell-cell communication via these channels is known to play an important role in the control of cell proliferation, embryonic development, cell differentiation, and the regulation of differentiated function in post-mitotic cells. Vertebrate gap junctions are composed of proteins derived from the connexin gene family, and our results indicate that gap junction formation and degradation are highly regulated via protein kinases at various stages of the assembly process and the cell cycle.

Ongoing studies include determination of the cellular localization of different connexin phosphorylation events and the specific serine substrates that are phosphorylated within connexins at different stages of the cell cycle. Thus, we attempt to link the activation of specific kinases to phosphorylation on a particular residue within the connexin protein and to connexin function in tissue including skin and heart. Our data indicates that kinases such as PKA, PKC, CK1, cdc2/cyclinB, MAP-K, Akt and others regulate specific steps of gap junction protein export, assembly, channel gating and degradation. To perform these studies of gap junction function, we utilize a variety of cell, molecular and biochemical techniques including super resolution microscopy, tracer microinjection and GFP chimeras to monitor gap junctions in living cells.