Synaptotagmin is an environmentally sensitive calcium ion sensor.
2010-09
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Synaptotagmin is an environmentally sensitive calcium ion sensor.
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2010-09
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Exocytosis of neurotransmitters into the presynaptic space is triggered by an influx of Ca2+. Synaptotagmin 1 (Syt1) mediates the fusion of the vesicular bilayer with the presynaptic bilayer through its interactions with Ca2+, phospholipid, and the fusion machinery. The exact mechanism for this information transduction, however, is not well understood. Syt1 contains two homologous binding domains, C2A and C2B, which are tethered to a neurotransmitter containing vesicle by a flexible linker region. We hypothesize that the entire Syt1 C2A domain (linker + C2A) is necessary to translate this binding information into a fusion response. To understand the cooperativity of binding in Syt1 C2A, we studied two commonly utilized C2A constructs. The short construct is simply the structural C2A domain (amino acids 140-265). The second construct possesses more of the flexible linker (amino acids 96-265). To thermodynamically compare the binding behavior between the two constructs, we studied the Ca2+ and phospholipid binding using steady state fluorescence and Ca2+ binding using ITC. The results were modeled by binding partition functions. The data are consistent with diminished linkage among the binding sites in the short construct. We conclude that the flexible linker domain serves more of an important biological function than tethering the C2 domains to the membrane.
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University of Minnesota M.S. thesis. September 2010. Major: Chemistry. Advisor: Prof. Anne Hinderliter. 1 computer file (PDF); vi, 63 pages.
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Murphy, Jesse Ray. (2010). Synaptotagmin is an environmentally sensitive calcium ion sensor.. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/102691.
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