Connexin and pannexin (hemi)channels in the liver

Abstract

The liver was among the first organs in which connexin proteins have been identified. Hepatocytes harbor connexin32 and connexin26, while non-parenchymal liver cells typically express connexin43. Connexins give rise to hemichannels, which dock with counterparts on adjacent cells to form gap junctions. Both hemichannels and gap junctions provide pathways for communication, via paracrine signaling or direct intercellular coupling, respectively. Over the years, hepatocellular gap junctions have been shown to regulate a number of liver-specific functions and to drive liver cell growth. In the last few years, it has become clear that connexin hemichannels are involved in liver cell death, particularly in hepatocyte apoptosis. This also holds true for hemichannels composed of pannexin1, a connexin-like protein recently identified in the liver. Moreover, pannexin1 hemichannels are key players in the regulation of hepatic inflammatory processes. The current paper provides a concise overview of the features of connexins, pannexins and their channels in the liver.

Keywords: cell death; connexin; gap junction; hemichannel; hepatocyte; inflammation; pannexin.

Figure 1

(A) Molecular architecture of gap junctions. Gap junctions are grouped in plaques at the cell plasma membrane surface of 2 adjacent cells and are composed of 12 connexin proteins organized as 2 hexameric hemichannels. The connexin protein consists of 4 membrane-spanning domains (TM), 2 extracellular loops (EL), 1 cytoplasmic loop (CL), 1 cytoplasmic aminotail (NT) and 1 cytoplasmic carboxytail (CT) (EC, extracellular; IC, intracellular) (Vinken et al., ; Decrock et al., 2009). (B) Structural comparison of connexins and pannexins (Chekeni et al., 2010).

Figure 2

Connexins and pannexins expressed in the liver. Schematic overview of the most relevant connexin and pannexin species expressed in rodent and human livers (Kumar and Gilula, ; Paul, ; Nicholson et al., ; Zhang and Nicholson, ; Chaytor et al., ; Bode et al., ; Fischer et al., ; Shiojiri et al., ; Xiao et al., 2012).