Elliot L. Hertzberg

Analysis of Gap Junctions

The focus of our research is functional and biochemical analysis of membrane proteins, especially connexins (Cxs), the family of proteins comprising gap junctions. The specific research projects analyze events responsible for establishment and regulation of gap junctional intercellular communication with an emphasis on the role(s) of posttranslational modifications such as phosphorylation and recently-discovered acetylation of Cx32 and Cx43. Others experiments suggest that Cx47 and, most likely other connexins, are acetylated as well. Acetylation of Cx32 and Cx47 appears to slow their turnover. Properties influenced by acetylation of Cx43 are not yet known and are subject of ongoing analyses.

Our studies utilize several cultured cell lines and primary cell cultures for connexin characterization under conditions where synthesis, modification and turnover can be modulated and communication can be assayed. These studies benefit from antibodies we have developed that are specific for individual connexins. Metabolic radiolabeling, including pulse-chase protocols, coupled with immunoprecipitation provide ready access in these systems to connexins in various stages of their life history.

Protein acetylation has long been established as a prominent mechanism working at several levels in the regulation of gene expression. The unanticipated finding of connexin acetylation raises questions about how widespread protein acetylation is and how this protein modification plays a role in other aspects of regulation of cell function. We are actively pursuing development of novel assays of protein acetylation in order to approach what appears to be a fundamental biological process that has been underappreciated in neuroscience and cell biology in general.

Selected Publications