Introduction to gap junctions
Gap junction mediated intercellular communication
Figure legend: Diagram of cells endowed with gap junction channels. A, Cells 1+2 can communicate by directly exchanging small molecules such as cAMP, cGMP, Ca+ and K+ (green arrows, dots) via a 'classical' arrangement of gap junctions (GJ) (holochannels in a plaque). B, Cell 3 has undocked hemichannels in the plasma membrane. Undocked hemichannels were thought to exist in a closed state until they docked to hemichannels in a neighbouring cell - presumably to prevent disruption of cellular homeostasis. Relatively recently it was discovered that hemichannels in the plasma membrane can be found in an open state. Open hemichannels allow small signalling molecules (green dots eg, ATP) to be released into the extracellular space where they can bind to, and activate, nearby receptors (red)(Romanov et al, 2007, Dando and Roper, 2009). Hence, cells 3+4 can communicate using a mix'n'match version of gap junction+ligand/receptor signalling. C, Innexin proteins have been detected in the nucleus of certain cell types (Ostrowski et al, 2008) but their role there has not been explored. It has been proposed that connexins might also be able to alter transcription following re-distribution to the nucleus (Dang et al. 2003)...although the only evidence is based on connexin fragments, so far.
Gap junction channel structure
Figure legend: Diagram of a gap junction composed of vertebrate connexin subunits. Invertebrate innexin subunits are believed to form channels with a similar overall structure (although there is virtually no available data supporting this). A single gap junction channel (holochannel) is composed of two hemichannels, one contributed from each of the docked cells. Each hemichannel is comprised of six connexin gap junction subunits (innexin subunits in the case of invertebrates). The hydrophilic holochannel pore allows passage of small molecules such as ions and second messengers directly from cell to cell. Holochannels can accumulate at distinct regions of the plasma membrane forming specialized 'plaque' structures (Plaques in salivary gland cells).
Intercellular communication is essential for the normal development of multicellular animals. Ligand/receptor and gap junction signalling are the two main mechanisms permitting cell-cell communication to take place. An understanding of gap junction mediated communication and its interaction with ligand/receptor pathways is therefore crucial for constructing an accurate model of development in normal and diseased tissues. Three distinct gap junction-forming protein families have been identified: Connexins (Cx) (Evans and Martin 2002), Pannexins (Px) (Bruzzone et al. 2003, Panchin et al. 2000) and Innexins (Inx) (Phelan et al. 1998). Connexin-based gap junctions have received the most research attention as they are present in vertebrates and underlie a number of human pathologies (Alldredge 2008). Connexins are not found in invertebrates where the role of gap junction signalling is mediated by members of the innexin protein family (Innexin family description). A brief compare-and-contrast table is provided below.