Gap junction alpha-1 protein–microtubule interface (Cx43–MT interface) (Cx43–MT interface)

Gap junction alpha-1 protein (Connexin 43 or Cx43) is a critical transmembrane protein that forms hemichannels and gap junctions, facilitating electrical and chemical coupling between cells, particularly in the ventricular myocardium (UniProt P17302). The Cx43–microtubule interface refers to the specific protein-protein interaction between the C-terminal tail of Cx43 and the microtubule network, which serves as a highway for the delivery of newly synthesized Cx43 to the plasma membrane (Shaw et al., 2007, Cell). This trafficking process is essential for maintaining the high density of gap junctions at intercalated discs required for rapid cardiac conduction. In pathological states like myocardial infarction or heart failure, this interface is often compromised, leading to the lateralization of Cx43 and subsequent arrhythmogenesis (Smyth et al., 2010, Journal of Cell Science). Therapeutic strategies targeting this interface, such as the JM2 peptide, aim to modulate Cx43-tubulin binding to prevent the sequestration of Cx43 in the cytoplasm or its mislocalization to lateral membranes, thereby preserving cardiac rhythm and reducing the risk of sudden cardiac death (Basheer et al., 2017, JACC: Basic to Translational Science). Beyond the heart, this interface is also a subject of interest in wound healing and oncology, where Cx43-mediated communication influences cell migration and tissue repair.

Other names

Connexin 43–microtubule interactionGJA1–tubulin binding siteCx43–TBD interactionConnexin 43–tubulin interface

Modulation of the protein-protein interaction between the Connexin 43 C-terminal tubulin-binding domain and microtubules to regulate gap junction hemichannel trafficking and assembly.