Dr. Beyer's laboratory is focused on understanding the regulation of intercellular communication as mediated by gap junction channels. Gap junctions are the specialized plasma membrane structures, which contain low resistance channels linking adjacent cells. In excitable tissues, they permit electrical coupling; in non-excitable tissues, they permit passage of small molecules involved in metabolic support, growth control, and embryogenesis. They may also facilitate drug metabolite delivery between cells. In migratory cells (such as macrophages), which also express these proteins, they may facilitate more transient interactions.

We have cloned cDNAs corresponding to gap junction proteins from a number of different tissues and species. These sequences demonstrate that there is a family of gap junction proteins (connexins) which are related in their transmembrane and extracellular regions, but which have unique cytoplasmic domains. We have also raised antibodies directed against specific domains within the connexin sequences. The cDNA and antibody regents are being used in a number of whole animal, tissue culture, and expression systems to investigate the structure and function of gap junctions and the regulation of intercellular communication. A major current effort is underway to elucidate the mechanisms of degradation of gap junctions and the importance of this process in the remodeling of cardiac cellular connections. The transfection of communication-deficient cells with connexin sequences has demonstrated connexin-specific channel properties, permeabilities, and regulation. Site-directed mutagenesis is being used to identify sites within the connexins important in determining gating and permeability properties. Another major effort in the laboratory (in collaboration with Dr. L. Philipson) focuses on the role and function of gap junctions in coupling beta cells in human and mouse islets. These channels likely coordinate electrical and calcium signaling and oscillations.