Tilting the balance between facilitatory and inhibitory functions of mammalian and Drosophila Complexins orchestrates synaptic vesicle exocytosis.
Tilting the balance between facilitatory and inhibitory functions of mammalian and Drosophila Complexins orchestrates synaptic vesicle exocytosis.
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DOI：
10.1016/j.neuron.2009.09.043
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发表时间：
2009-11-12
期刊：
影响因子：
16.2
通讯作者：
Rosenmund, Christian
中科院分区：
文献类型：
--
作者：
Xue, Mingshan;Lin, Yong Qi;Pan, Hongling;Reim, Kerstin;Deng, Hui;Bellen, Hugo J.;Rosenmund, Christian
snare介导的突触胞吐是由促进和抑制机制协调的。复杂蛋白（一个SNARE复合物结合蛋白家族）在小鼠和果蝇体内的基因缺失对神经递质释放的影响明显相反，导致了对复杂蛋白功能的相互矛盾的假设。用不同的融合分析和络合素进行的重构实验也产生了相互矛盾的结果。因此，我们进行了跨物种拯救实验，比较小鼠和果蝇复合蛋白在小鼠和果蝇突触中的功能。我们发现小鼠和果蝇复杂素采用保守的机制来调节胞吐，尽管它们对神经递质释放的总体影响截然不同。这两种络合蛋白都含有促进或抑制突触囊泡融合的不同结构域，并且每种促进或抑制功能的强度在小鼠和果蝇络合蛋白之间存在显著差异。我们的研究结果表明，促进和抑制功能平衡的相对转变导致小鼠和果蝇复杂素在体内对神经递质释放的不同调节，这与之前不相容的发现相一致。
SNARE-mediated synaptic exocytosis is orchestrated by facilitatory and inhibitory mechanisms. Genetic ablations of Complexins, a family of SNARE complex–binding proteins, in mice and Drosophila cause apparently opposite effects on neurotransmitter release, leading to contradictory hypotheses of Complexin function. Reconstitution experiments with different fusion assays and Complexins also yield conflicting results. We therefore performed cross-species rescue experiments to compare the functions of murine and Drosophila Complexins in both mouse and fly synapses. We found that murine and Drosophila Complexins employ conserved mechanisms to regulate exocytosis despite their strikingly different overall effects on neurotransmitter release. Both Complexins contain distinct domains that facilitate or inhibit synaptic vesicle fusion, and the strength of each facilitatory or inhibitory function differs significantly between murine and Drosophila Complexins. Our results show that a relative shift in the balance of facilitatory and inhibitory functions results in differential regulation of neurotransmitter release by murine and Drosophila Complexins in vivo, reconciling previous incompatible findings.
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DOI：
10.1126/science.1166500
发表时间：
2009-01-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Giraudo CG;Garcia-Diaz A;Eng WS;Chen Y;Hendrickson WA;Melia TJ;Rothman JE
通讯作者：
Rothman JE
影响因子：
25
作者：
Huntwork, Sarah;Littleton, J. Troy
通讯作者：
Littleton, J. Troy
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
56.9
作者：
Lois, C;Hong, EJ;Baltimore, D
通讯作者：
Baltimore, D
影响因子：
4.8
作者：
Pabst, S;Hazzard, JW;Fasshauer, D
通讯作者：
Fasshauer, D