Calcium accelerates SNARE-mediated lipid mixing through modulating α-synuclein membrane interaction.
Calcium accelerates SNARE-mediated lipid mixing through modulating α-synuclein membrane interaction.
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DOI：
10.1016/j.bbamem.2018.03.025
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
Zeting Zhang;Xin Jiang;Danrui Xu;Wenwen Zheng;Maili Liu;Conggang Li
中科院分区：
文献类型：
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作者：
Zeting Zhang;Xin Jiang;Danrui Xu;Wenwen Zheng;Maili Liu;Conggang Li
α-突触核蛋白参与帕金森病，其与细胞膜的相互作用对其病理和生理功能至关重要。我们已经证明Ca2+可以调节α-突触核蛋白膜相互作用，但Ca2+在调节α-突触核蛋白膜相互作用中的生理作用仍未被探索。基于α-突触核蛋白抑制膜融合且其抑制作用与其膜结合高度相关的研究结果，我们采用溶液态核磁共振（NMR）波谱和整体荧光融合实验表明，Ca2+可以通过破坏α-突触核蛋白膜相互作用来调节α-突触核蛋白对SNARE介导的膜融合的抑制作用，从而加速SNARE介导的膜融合。这些结果表明Ca2+对膜的调节作用介导α-突触核蛋白的正常功能，这对于帕金森病的研究具有重要意义。
α-Synuclein is involved in Parkinson's disease, and its interaction with cell membrane is vital to its pathological and physiological functions. We have shown that Ca2+can regulate α-synuclein membrane interaction, but the physiological role of Ca2+in modulating α-synuclein membrane interaction is still unexplored. Based on the previous findings that α-synuclein inhibits membrane fusion and its inhibitory effect is highly related to its membrane binding, here we employed solution state Nuclear Magnetic Resonance (NMR) spectroscopy and the ensemble fluorescence fusion assay to show that Ca2+can modulate the inhibitory effect of α-synuclein on SNARE-mediated membrane fusion through disrupting α-synuclein membrane interaction, resulting in acceleration of SNARE-mediated membrane fusion. These results suggest a modulatory effect of Ca2+on membrane mediated normal function of α-synuclein, which of importance for the study of the Parkinson's disease.