Gap junction trafficking

Stable Identifier
R-HSA-190828
Type
Pathway
Species
Homo sapiens
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Gap junctions are intercellular communication channels formed from Cx (connexin) protein subunits (see Segretain and Falk 2004 and Evans et al. 2006 for comprehensive reviews). Connexins are transported to the plasma membrane after oligomerizing into hexameric assemblies called hemichannels (CxHcs) or connexons. Connexons dock head-to-head in the extracellular space with opposing hexameric channels located in the plasma membranes of neighbouring cells. The double membrane channel or gap junction generated directly links the cytoplasms of interacting cells and facilitates the integration and co-ordination of cellular signalling, metabolism, secretion and contraction. In addition to their role in intercellular communication, connexon hemichannels coordinate the release of ATP, glutamate, NAD+ and prostaglandin E2 from the cells. CxHcs open in response to various types of external changes, including mechanical, shear, ionic and ischaemic stress.

The trafficking of gap junctions involves (1) synthesis of connexin polypeptides at endoplasmic reticulum membranes, (2) oligomerization into homomeric- and heteromeric gap junction connexons (hemi-channels), (3) passage through the Golgi stacks, (4) intracellular storage within Trans Golgi membranes, (5) trafficking along microtubules, (6) insertion of connexons into the plasma membrane, (7) lateral diffusion of connexons in the plasma membrane, (8) aggregation of individual gap junction channels into plaques, (9) stabilization of peripheral microtubule plus-ends by binding to Cx43-based gap junctions, (10) internalization of the channel plaque leading to cytoplasmic annular junctions, and (11) complete degradation via lysosomal and proteasomal pathways (see Segretain and Falk 2004). Aspects of gap assembly are described here.

Literature References
PubMed ID Title Journal Year
8522583 Gap junction turnover, intracellular trafficking, and phosphorylation of connexin43 in brefeldin A-treated rat mammary tumor cells

Laird, DW, Castillo, M, Kasprzak, L

J Cell Biol 1995
15033576 Regulation of connexin biosynthesis, assembly, gap junction formation, and removal

Segretain, D, Falk, MM

Biochim Biophys Acta 2004
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