| Health / Medical Topics |
Synaptic Vesicle Endocytosis Pathway
Reliable neurotransmitter release requires the presence of sufficient numbers of synaptic vesicles. The process of synaptic vesicle endocytosis (SVE) is coordinated by a group of proteins called dephosphins. The current set of seven known dephosphins are nerve terminal proteins with little or no structural homology but satisfy two essential criteria: they are essential for SVE and they are rapidly and coordinately dephosphorylated in response to a calcium influx through voltage-dependent calcium channels. The calcium signal is mediated by calmodulin (CaM) and calcineurin. Each dephosphin plays an essential role in overlapping phases or segments of the cycle. The four phases of SVE are nucleation, invagination, fission and uncoating. The nucleation phase initiates with the activation of CaM/Calcineurin and the subsequent dephosphorylation of AP180. AP180 and clathrin are then recruited to the membrane by AP2 and PtdIns(4,5)P2. Nucleation is completed by the addition of epsin and eps15. Invagination proceeds with the formation of the amphiphysin1/2 heterodimer and its addition to the maturing vesicle surface complexes. The final components, dynamin and synaptojanin, are recruited to the budding vesicle by the amphiphysin1/2 heterodimer. Dynamin forms a complete ring around the vesicle neck and completes fission via its PtdIns(4,5)P2 stimulated GTPase activity. After internalization the vesicle is quickly uncoated, in a process believed to be mediated by synaptojanin, and is accompanied by the disassembly of clathrin. (NCI Thesaurus/BIOCARTA)
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