Understanding and Engineering Gap Junctions

We explore the compositional diversity of gap junctions, focusing on the 21 human connexin (Cx) isoforms and their ability to mix and match within and across tissues. By characterizing which isoforms are able to interact to form functional gap junction channels, we can begin to understand how different isoforms contribute unique properties to gap junction intercellular communication (GJIC). Ultimately, we aim to understand the molecular mechanisms that drive Cx isoform specificity of ionic and small molecule exchange. This research seeks to uncover how gap junction diversity impacts tissue physiology and how mutations or misregulation of Cx proteins contribute to diseases such as deafness, epilepsy, neurodegeneration, and cancer.

Our lab investigates the dynamic regulation of gap junctions, particularly the roles of plaques (large clusters of gap junction channels) and connexosomes (specialized vesicles mediating the turnover of fully-docked gap junction channels). We aim to understand how these structures regulate channel assembly, disassembly, and recycling, as well as their influence on GJIC in health and disease. By characterizing the mechanisms governing these processes, we hope to provide new insights into the maintenance and modulation of intercellular communication.

HEK 293FT cells transiently transfected with fluorescently-tagged connexin protein constructs label gap junction plaques (i.e., linear structures in the image) as well as internalized connexosomes (boxed and inset). The inset image clearly indicates that the vesicular structure in one cell originated from another cell and contains another cell’s cytoplasms – identifying it as a connexosome.