PathwayType: signaling
Organ: generic
Pathway_Author: A. Nesterova ORCID:0000-0002-9448-8101
Organ_System: generic
Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-352448de-805b-46d5-8a8d-f89bc72e8ea5
Tissue: generic
Notes: Headnote: The gap junctions are specialized contacts between cells that mediate the direct exchange of ions and metabolites under approximately 1000Da between the cells. Signaling description: The gap junctions of vertebrates are composed of the connexin family. One connexon consists of six connexin molecules. Gap junction connexon channels are formed from both heterotypic (different connexins in opposed cells) and heteromeric (different connexins in the same cell) channels. There are different types of interactions between connexins. GJA1 is the most widespread connexin in mammalian cells and can oligomerize with other connexins such as GJB2 (hepatocytes and keratinocytes), GJB3 (keratinocytes), and GJC1 (cardiomyocytes). Gap junction channels are unusual among ion channels since they typically remain open at rest and only close under specific circumstances. They close in response to a number of stimuli that generally reflect the poor health of a cell including low pH, high intracellular Ca2+ concentration and voltage differences between cells, and a number of physiological stimuli that are typically associated with increased cell division. Gap junctional communication is controlled by neurotransmitters, cytokines, growth factors, and other bioactive compounds such as LPA. Outcome effects: These biomolecules activate downstream kinases including PKG, PKA, PKC, casein kinase, MAPK3, MAPK1, and MAPK7. The kinase activators then significantly increase levels of GJA1 phosphorylation at specific sites leading to channel opening. When dopamine/DRD1 and noradrenaline/ADRB1 are coupled to G-protein it leads to cAMP production. In contrast, when dopamine/DRD2 binds to G-protein, ADCY activity is blocked and cAMP production is reduced. Other neurotransmitters such as serotonin and glutamate activate PLC which leads to the generation of IP3 and diacylglycerol. Diacylglycerol activates PKC, whereas the association of IP3 and IP3 receptor (ITPR1) promotes the release of Ca2 from endoplasmic reticulum. Gating is also controlled by a short-lived free radical gas NO through the ADCY-cGMP route activating PKG.
NodeType: Pathway
Description: Gap junctions are specialized contacts between cells that mediate the direct exchange of ions and metabolites under approximately 1000Da between cells in contact. Pathway is built manually using published studies.
Source: Cell Process
CellType: generic
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