Comparative analysis of Drosophila and mammalian complexins as fusion clamps and facilitators of neurotransmitter release.
Comparative analysis of Drosophila and mammalian complexins as fusion clamps and facilitators of neurotransmitter release.
复制标题
DOI：
10.1016/j.mcn.2010.07.012
复制
发表时间：
2010-12
影响因子：
3.5
通讯作者：
Littleton, J. Troy
中科院分区：
文献类型：
--
作者：
Cho, Richard W.;Song, Yun;Littleton, J. Troy
SNARE结合蛋白复合体(CPX)已被证明调节突触小泡融合。先前的研究与CPX的功能一致，既可以作为突触小泡融合钳来防止过早的胞吐，也可以作为促进剂直接刺激释放。在这里，我们使用果蝇神经肌肉接头作为突触模型，研究了无脊椎动物和哺乳动物CPX亚型在调节神经递质释放中的保守作用。我们发现，作为融合钳的作用需要CPX结合SNARE。所有四种哺乳动物CPx蛋白(MCpx)都被证明可以促进释放，当在果蝇acpx缺失突变体中表达时，也可以作为融合钳使用，尽管它们的钳制能力在不同的亚型之间有所不同。此外，与mCpx IV或果蝇CPx相比，mCpx I、II或III亚型的表达显著增强了诱导释放。络合蛋白异构体在夹持和促进性质上的差异可以部分归因于C-末端膜系留结构域的不同。我们的发现表明，复合体作为融合钳和融合促进器的功能在进化过程中是保守的，并且这些作用在同一亚型内和不同亚型之间是可遗传分离的。
The SNARE-binding protein complexin (Cpx) has been demonstrated to regulate synaptic vesicle fusion. Previous studies are consistent with Cpx functioning either as a synaptic vesicle fusion clamp to prevent premature exocytosis, or as a facilitator to directly stimulate release. Here we examined conserved roles of invertebrate and mammalian Cpx isoforms in the regulation of neurotransmitter release using the Drosophila neuromuscular junction as a model synapse. We find that SNARE binding by Cpx is required for its role as a fusion clamp. All four mammalian Cpx proteins (mCpx), which have been demonstrated to facilitate release, also function as fusion clamps when expressed in Drosophilacpx null mutants, though their clamping abilities varies between isoforms. Moreover, expression of mCpx I, II or III isoforms dramatically enhance evoked release compared to mCpx IV or Drosophila Cpx. Differences in the clamping and facilitating properties of complexin isoforms can be partially attributed to differences in the C-terminal membrane tethering domain. Our findings indicate that the function of complexins as fusion clamps and facilitators of fusion are conserved across evolution, and that these roles are genetically separable within an isoform and across different isoforms.
登录
查看更多内容
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：
64.5
作者：
GEPPERT, M;GODA, Y;SUDHOF, TC
通讯作者：
SUDHOF, TC
影响因子：
64.5
作者：
SOLLNER, T;BENNETT, MK;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：
3.5
作者：
Seiler, Florian;Malsam, Joerg;Krause, Jean Michel;Soellner, Thomas H.
通讯作者：
Soellner, Thomas H.