Figure 3.

Synthesis and intracellular trafficking (left cell) and degradation (right cell) of connexins. Connexins are synthesized at the endoplasmic reticulum but are oligomerized into hemichannels at the cis-Golgi apparatus or at the trans-Golgi network (TGN). Transport to the plasma membrane occurs predominantly through microtubules and motor proteins such as kinesin, but actin may also play an important role. Direct delivery of vesicles containing hemichannels may also occur. Cx43 reaches mitochondria using the TOM/TIM system of protein import, in an Hsp90-dependent manner. N-terminally truncated isoforms can be found at the cytoplasm and nucleus. Degradation occurs through formation a double-membrane structure, termed connexosome. Connexosomes can then be targeted to the endolysosomal or the autophagosomal pathways. Connexins can also be degraded after synthesis at the endoplasmic reticulum by the proteasome. Release of microvesicles and exosomes containing connexins is also depicted. GJ indicates gap junctions. Created with Biorender.com (accessed on 15 April 2021). Modified from [8,12,27].