The cellular life of pannexins

Abstract

The mammalian pannexin family of channel-forming proteins consisting of Panx1, Panx2, and Panx3 has received considerable attention in the last 10 years given their newly discovered physiological roles in development and disease. Pannexins exhibit diverse subcellular profiles indicating that they may serve distinct roles in cells and tissues of different origin. This complexity in cellular residencies may be rooted in the fact that pannexin genes consist of multiple exons that have led to the identification of several splice variants. Additionally, post-translational modifications, especially N-glycosylation, appear to be important in regulating trafficking and intermixing of pannexin family members increasing the diversity of assembled channels. These long-lived membrane proteins are typically trafficked through the classical secretory pathway before reaching the plasma membrane although Panx2 tends to often be retained in intracellular compartments. Trafficking, stability, and function of pannexins likely enlist the services of an interactome that continues to expand. The research field has been amazed by the fact that Panx1 null mice are generally healthy with distinct phenotypes only being revealed when mutant mice encounter additional stress or have comorbidities. The emerging field of pannexin biology has also begun to explore the relationships and potential cross-talk between pannexin channels and connexin hemichannels. It is imperative to dissect the different constituents of the channels and the molecules that pass through these distinct channel types. Finally, as witnessed in connexin biology throughout the 90s, the field awaits to see if germline mutations in the genes that encode pannexins also cause disease.

Trypanosoma cruzi Infection Induces Pannexin-1 Channel Opening in Cardiac Myocytes

“…15 Panx1 has been detected preferentially in the surface membrane but has also been found in intracellular compartments in rat atrial and ventricular primary cardiomyocytes. 24,25 Unfortunately, our results do not allow us to identify if this greater expression occurs in the plasma membrane or at intracellular compartments of the cells.…”

N-Glycosylation Regulates Pannexin 2 Localization but Is Not Required for Interacting with Pannexin 1

“…A previous study in murine postnatal hippocampal neural progenitor cells (NPC)s [ 17 ] showed that treatment with glycosidases had no effect on endogenous Panx2 electrophoretic mobility, suggesting that they were un-glycosylated. That study relied on antibody detection of endogenous Panx2, and the protein bands identified were of lower molecular weight than the predicted full-length Panx2 used in this study (677 aa, [ 39 ]). Further studies are needed to determine first, if the expression of certain un-glycosylated endogenous isoforms of Panx2 is cell-type specific, and second, whether glycosylation has measurable effects on the Panx2 cellular function.…”

Connexin and pannexin channels in cancer

“…Therefore, our understanding of the role of these two isoforms in cancer is limited. Panx3 plays a role in proliferation and differentiation of cells in skin, cartilage and bone [ 182 ], so we predict that we will soon learn more about a potential role for Panx3 in skin cancer and osteosarcomas. Panx2 has been proposed to play an important role as a tumour suppressor in brain tumours and hepatocellular carcinomas (Table 2 ).…”