Study of the effect of α-Synuclein on SNARE-mediated membrane fusion
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The Department of Biochemistry, Biophysics, and Molecular Biology was founded to give students an understanding of life principles through the understanding of chemical and physical principles. Among these principles are frontiers of biotechnology such as metabolic networking, the structure of hormones and proteins, genomics, and the like.
History
The Department of Biochemistry and Biophysics was founded in 1959, and was administered by the College of Sciences and Humanities (later, College of Liberal Arts & Sciences). In 1979 it became co-administered by the Department of Agriculture (later, College of Agriculture and Life Sciences). In 1998 its name changed to the Department of Biochemistry, Biophysics, and Molecular Biology.
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1959–present
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- Department of Biochemistry and Biophysics (1959–1998)
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- College of Agriculture and Life Sciences (parent college)
- College of Liberal Arts and Sciences (parent college)
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Abstract
Neurotransmitter release is a precisely orchestrated process in terms of time and space in neuron. SNAREs have been identified to function as the basic machinery mediating membrane fusion during neutotransmitter release. Many forms of neurodegeneration initiate presynaptically, but few of their molecular mechanisms have been revealed clearly. α-Synuclein (α-Syn) is a highly conserved synaptic vesicle-associated protein. Aggregation of α-Syn is a major component of the Lewy bodies, which is characteristic of Parkinson's disease (PD). We studied the effect of α-Syn on SNARE-mediated membrane fusion using fluorescent methods. Bulk lipid mixing assay shows that α-Syn has a role of inhibition in fusion and this effect requires phosphatidylserine (PS) on the vesicles. Disease related α-Syn mutants, A30P and E46K, shows higher inhibition effect on the lipid mixing than wild type. Synaptotagmin-1 (Syt-1) is a Ca2+ sensor localized to synaptic vesicles and regulates neuronal exocytosis. C2AB, a soluble model of Syt-1 that lacks the transmembrane region, is shown here to accelerate the FRET significantly. This acceleration effect of lipid mixing also needs PS on the vesicles. α-Syn can inhibit C2AB's stimulatory effect to a large extent. Thus, α-Syn can inhibit SNARE-mediated membrane fusion event.