PMC:7573190 / 13696-16027
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7573190","sourcedb":"PMC","sourceid":"7573190","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7573190","text":"SNARE-mediated exocytosis\nInsulin vesicle exocytosis is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins (Gaisano, 2017[37]), which can be divided into two categories: vesicle (v)-SNAREs from the vesicle membrane, and target (t)-SNAREs from the target membrane. t-SNARE, includes the syntaxin and synaptosome associated protein-25 (SNAP-25) families, while v-SNAREs refers to vesicle-associated membrane proteins (VAMPs) (Jewell et al., 2010[58]).\nTethering is the initial contact between a vesicle and the plasma membrane and is mediated by the exocyst complex (Liu and Guo, 2012[74]; Martin-Urdiroz et al., 2016[83]), which is a conserved octameric complex that tethers exocytic vesicles to the plasma membrane prior to fusion. This complex contains Sec (for secretion) and Exo (for exocyst related) proteins (Liu and Guo, 2012[74]; Xie et al., 2013[137]; Martin-Urdiroz et al., 2016[83]). In docking and attachment to the plasma membrane, Munc18 (mammalian uncoordinated-18) binds to syntaxin and recruits SNAP-25 to the plasma membrane (Shibasaki et al., 2014[114]). Rab3A, a small GTPase, with its interacting partner (Rim2α) binds to Munc18 and plays an important role in docking (Shibasaki et al., 2014[114]). v-SNARE VAMP-2 (also known as synaptobrevin) pairs with the t-SNAREs syntaxin and SNAP-23/25 to form the SNARE core complex. Prior to formation of the SNARE complex, the accessory protein Sec1/Munc18 provides a bridge between v-SNARE and t-SNARE so that the space between membranes is closed (Martin-Urdiroz et al., 2016[83]). Munc18 proteins are essential regulators of SNARE-mediated exocytosis and reduction in Munc18/SNARE complex has been implicated in the loss of first phase of insulin secretion in type 2 diabetes (Gaisano, 2014[36]). Priming, in which granules become ready for the fusion process, is an ATP-dependent reaction necessary for exocytosis (Renström, 2011[103]; Shibasaki et al., 2014[114]). In priming, SNARE proteins form a complex in preparation for Ca2+-triggered fusion (Gaisano, 2014[36]). Following Ca2+ entry, synaptotagmins act as Ca2+ sensors (Sollner, 2003[117]) and also promote fusion pore formation (Gaisano, 2014[36]) leading to insulin secretion. The primary Ca2+ sensor in β-cells is synaptotagmin-7 (Roder et al., 2016[106]).","divisions":[{"label":"title","span":{"begin":0,"end":25}},{"label":"p","span":{"begin":26,"end":497}}],"tracks":[{"project":"MyTest","denotations":[{"id":"33088259-20053958-29829732","span":{"begin":492,"end":494},"obj":"20053958"},{"id":"33088259-21997494-29829733","span":{"begin":631,"end":633},"obj":"21997494"},{"id":"33088259-27148529-29829734","span":{"begin":664,"end":666},"obj":"27148529"},{"id":"33088259-21997494-29829735","span":{"begin":880,"end":882},"obj":"21997494"},{"id":"33088259-23844030-29829736","span":{"begin":902,"end":905},"obj":"23844030"},{"id":"33088259-27148529-29829737","span":{"begin":936,"end":938},"obj":"27148529"},{"id":"33088259-27148529-29829738","span":{"begin":1588,"end":1590},"obj":"27148529"},{"id":"33088259-24746186-29829739","span":{"begin":1804,"end":1806},"obj":"24746186"},{"id":"33088259-24746186-29829740","span":{"begin":2078,"end":2080},"obj":"24746186"},{"id":"33088259-12893529-29829741","span":{"begin":2156,"end":2159},"obj":"12893529"},{"id":"33088259-24746186-29829742","span":{"begin":2216,"end":2218},"obj":"24746186"},{"id":"33088259-27621482-29829743","span":{"begin":2325,"end":2328},"obj":"27621482"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"33088259-20053958-29829732","pred":"source","obj":"MyTest"},{"subj":"33088259-21997494-29829733","pred":"source","obj":"MyTest"},{"subj":"33088259-27148529-29829734","pred":"source","obj":"MyTest"},{"subj":"33088259-21997494-29829735","pred":"source","obj":"MyTest"},{"subj":"33088259-23844030-29829736","pred":"source","obj":"MyTest"},{"subj":"33088259-27148529-29829737","pred":"source","obj":"MyTest"},{"subj":"33088259-27148529-29829738","pred":"source","obj":"MyTest"},{"subj":"33088259-24746186-29829739","pred":"source","obj":"MyTest"},{"subj":"33088259-24746186-29829740","pred":"source","obj":"MyTest"},{"subj":"33088259-12893529-29829741","pred":"source","obj":"MyTest"},{"subj":"33088259-24746186-29829742","pred":"source","obj":"MyTest"},{"subj":"33088259-27621482-29829743","pred":"source","obj":"MyTest"}]},{"project":"2_test","denotations":[{"id":"33088259-20053958-29829732","span":{"begin":492,"end":494},"obj":"20053958"},{"id":"33088259-21997494-29829733","span":{"begin":631,"end":633},"obj":"21997494"},{"id":"33088259-27148529-29829734","span":{"begin":664,"end":666},"obj":"27148529"},{"id":"33088259-21997494-29829735","span":{"begin":880,"end":882},"obj":"21997494"},{"id":"33088259-23844030-29829736","span":{"begin":902,"end":905},"obj":"23844030"},{"id":"33088259-27148529-29829737","span":{"begin":936,"end":938},"obj":"27148529"},{"id":"33088259-27148529-29829738","span":{"begin":1588,"end":1590},"obj":"27148529"},{"id":"33088259-24746186-29829739","span":{"begin":1804,"end":1806},"obj":"24746186"},{"id":"33088259-24746186-29829740","span":{"begin":2078,"end":2080},"obj":"24746186"},{"id":"33088259-12893529-29829741","span":{"begin":2156,"end":2159},"obj":"12893529"},{"id":"33088259-24746186-29829742","span":{"begin":2216,"end":2218},"obj":"24746186"},{"id":"33088259-27621482-29829743","span":{"begin":2325,"end":2328},"obj":"27621482"}],"attributes":[{"subj":"33088259-20053958-29829732","pred":"source","obj":"2_test"},{"subj":"33088259-21997494-29829733","pred":"source","obj":"2_test"},{"subj":"33088259-27148529-29829734","pred":"source","obj":"2_test"},{"subj":"33088259-21997494-29829735","pred":"source","obj":"2_test"},{"subj":"33088259-23844030-29829736","pred":"source","obj":"2_test"},{"subj":"33088259-27148529-29829737","pred":"source","obj":"2_test"},{"subj":"33088259-27148529-29829738","pred":"source","obj":"2_test"},{"subj":"33088259-24746186-29829739","pred":"source","obj":"2_test"},{"subj":"33088259-24746186-29829740","pred":"source","obj":"2_test"},{"subj":"33088259-12893529-29829741","pred":"source","obj":"2_test"},{"subj":"33088259-24746186-29829742","pred":"source","obj":"2_test"},{"subj":"33088259-27621482-29829743","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"MyTest","color":"#ecdd93","default":true},{"id":"2_test","color":"#c393ec"}]}]}}