Lipid modulation of calcium flux through CaV2.3 regulates acrosome exocytosis and fertilization.
Lipid modulation of calcium flux through CaV2.3 regulates acrosome exocytosis and fertilization.
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DOI：
10.1016/j.devcel.2014.01.005
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发表时间：
2014-02-10
影响因子：
11.8
通讯作者：
Travis, Alexander J.
中科院分区：
文献类型：
--
作者：
Cohen, Roy;Buttke, Danielle E.;Asano, Atsushi;Mukai, Chinatsu;Nelson, Jacquelyn L.;Ren, Dongjun;Miller, Richard J.;Cohen-Kutner, Moshe;Atlas, Daphne;Travis, Alexander J.
对细胞功能的膜脂调节知之甚少。在发育早期，甾醇外流和神经节苷脂GM1通过未知的机制调节精子顶体胞吐和受精能力。在这里，我们证明了类固醇外流和GM1的局部浓缩通过CaV2.3触发了AE所必需的钙内流，其在精子中的活性一直存在很大争议。缺乏CaV2.3‘S成孔α1E亚基的精子表现出钙离子反应改变，AE降低，并具有较强的亚生育表型。令人惊讶的是，声发射依赖于通过CaV2.3的通量编码的时空信息--而不仅仅是钙波的存在/幅度。通过对非洲爪哇卵母细胞精子和电压钳的研究，我们确定了Gm1/CaV2.3相互作用的分子机制，需要Gm1‘S脂肪和糖成分以及CaV2.3’Sα1E和α2δ亚基。我们的结果提供了对膜脂调节钙离子通量的机制的理解，从而提供了钙依赖的细胞和发育过程，如胞吐和受精的机制。
Membrane lipid regulation of cell function is poorly understood. In early development, sterol efflux and the ganglioside GM1 regulate sperm acrosome exocytosis (AE) and fertilization competence through unknown mechanisms. Here, we show that sterol efflux and focal enrichment of GM1 trigger Ca2+ influx necessary for AE through CaV2.3, whose activity has been highly controversial in sperm. Sperm lacking CaV2.3’s pore-forming α1E subunit showed altered Ca2+ responses, reduced AE, and a strong sub-fertility phenotype. Surprisingly, AE depended on spatio-temporal information encoded by flux through CaV2.3—not merely the presence/ amplitude of Ca2+ waves. Using both studies in sperm and voltage clamp of Xenopus oocytes, we define a molecular mechanism for GM1/CaV2.3 regulatory interaction, requiring GM1’s lipid and sugar components and CaV2.3’s α1E and α2δ subunits. Our results provide mechanistic understanding of membrane lipid regulation of Ca2+ flux and therefore Ca2+-dependent cellular and developmental processes such as exocytosis and fertilization.
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影响因子：
3.8
作者：
Bennett, E;Urcan, MS;Levinson, SR
通讯作者：
Levinson, SR
影响因子：
2.5
作者：
Bar-Yehuda, Dan;Korngreen, Alon
通讯作者：
Korngreen, Alon
影响因子：
5.3
作者：
Davies, Anthony;Douglas, Leon;Dolphin, Annette C.
通讯作者：
Dolphin, Annette C.
DOI：
10.1073/pnas.1018202108
发表时间：
2011-03-22
影响因子：
11.1
作者：
Jin, Mayuko;Fujiwara, Eiji;Hirohashi, Noritaka
通讯作者：
Hirohashi, Noritaka
影响因子：
5.6
作者：
Jimenez-Gonzalez, M C;Gu, Y;Kirkman-Brown, J;Barratt, C L R;Publicover, S
通讯作者：
Publicover, S