Gap junction-dependent and -independent functions of connexin43 in biology

Authors: ZHU, YI - Children'S Nutrition Research Center (CNRC)

Submitted to: Biology
Publication Type: Review Article
Publication Acceptance Date: 2/10/2022
Publication Date: 2/11/2022
Citation: Zhu, Y. 2022. Gap junction-dependent and -independent functions of connexin43 in biology. Biology. 11(2):283. https://doi.org/10.3390/biology11020283.
DOI: https://doi.org/10.3390/biology11020283

Interpretive Summary:

Technical Abstract: Connexin43 is one of the 21 members of a large protein family that forms intercellular gap junction complexes. It plays a critical role in development by allowing two adjacent cells to exchange cellular content. Mouse deletion studies have demonstrated its critical roles in many organs, including cardiac muscle, blood vessels, bone, adipose tissue and more. However, as the most expressed and most studied connexin in the family, Connexin43 surprisingly shows many gap-junction-independent roles, spanning from the forming of hemichannels, to regulating membrane trafficking, to regulating mitochondrial function. Connexin43 is also unique in the family by forming many smaller polypeptides through alternative utilization of its mRNA molecule or cleavage of the translated full-length protein. This review summarizes recent advances on Connexin43's gap-junction-dependent and -independent functions in physiology. The knowledge will expand our understanding of how a gene grows its function by multiplexing its mRNA and protein. In the end, this may also guide us to develop Connexin43-based therapy for metabolic conditions, cancer, and other related diseases.