PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes.
PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes.
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PIP5激酶调节细胞毒性淋巴细胞的靶向颗粒分泌膜磷酸肌醇和肌动蛋白组成。
DOI：
10.1016/j.immuni.2018.08.017
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发表时间：
2018-09-18
期刊：
影响因子：
32.4
通讯作者：
Griffiths GM
中科院分区：
文献类型：
--
作者：
Gawden-Bone CM;Frazer GL;Richard AC;Ma CY;Strege K;Griffiths GM
细胞毒性T淋巴细胞（CTL）如何感知T细胞受体（TCR）信号传导以使质膜区域专门用于颗粒分泌尚不清楚。在这里，我们证明，免疫突触的形成导致质膜的磷酸肌醇组成的快速局部变化，既减少磷酸肌醇-4-磷酸（PI（4）P），PI（4，5）P2和PI（3，4，5）P3和增加二酰基甘油（DAG）和PI（3，4）P2在突触形成的前2分钟内。这些变化减少了突触上的负电荷，触发了补充PI（4，5）P2所需的静电结合的PIP 5激酶的释放。随着PI（4，5）P2降低，肌动蛋白从膜上耗尽，允许分泌。PIP 5 K β在突触上的强制定位阻止了肌动蛋白的消耗，阻断了中心体的对接和分泌。因此，PIP 5 Ks作为TCR激活的分子传感器，控制突触中的肌动蛋白募集，确保TCR信号传导和CTL分泌之间的精确协调。免疫突触形成触发膜组成和电荷的快速变化PIP 5 K是TCR激活的分子传感器，并在突触处迅速耗尽PIP 5 K分布控制免疫突触中的肌动蛋白募集膜特化控制中心体对接和分泌的可及性Gawden-Bone et al.显示在免疫突触形成期间，突触处PIP 5 K的快速消耗触发膜组成和肌动蛋白动力学的后续变化，以建立局部颗粒分泌区。
How cytotoxic T lymphocytes (CTLs) sense T cell receptor (TCR) signaling in order to specialize an area of plasma membrane for granule secretion is not understood. Here, we demonstrate that immune synapse formation led to rapid localized changes in the phosphoinositide composition of the plasma membrane, both reducing phosphoinositide-4-phosphate (PI(4)P), PI(4,5)P2, and PI(3,4,5)P3 and increasing diacylglycerol (DAG) and PI(3,4)P2 within the first 2 min of synapse formation. These changes reduced negative charge across the synapse, triggering the release of electrostatically bound PIP5 kinases that are required to replenish PI(4,5)P2. As PI(4,5)P2 decreased, actin was depleted from the membrane, allowing secretion. Forced localization of PIP5Kβ across the synapse prevented actin depletion, blocking both centrosome docking and secretion. Thus, PIP5Ks act as molecular sensors of TCR activation, controlling actin recruitment across the synapse, ensuring exquisite co-ordination between TCR signaling and CTL secretion. Immune synapse formation triggers rapid changes in the membrane composition and charge PIP5K is a molecular sensor of TCR activation and is rapidly depleted at the synapse PIP5K distribution controls actin recruitment across the immune synapse Membrane specialization controls accessibility for centrosome docking and secretion Gawden-Bone et al. show that during immune synapse formation, rapid depletion of PIP5K at the synapse triggers subsequent changes in membrane composition and actin dynamics to establish a zone of localized granule secretion.
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影响因子：
46.9
作者：
Ma, Yuanqing;Yamamoto, Yui;Gaus, Katharina
通讯作者：
Gaus, Katharina
影响因子：
5.6
作者：
Lai, Chun-Liang;Srivastava, Anand;Pilling, Carissa;Chase, Anna R.;Falke, Joseph J.;Voth, Gregory A.
通讯作者：
Voth, Gregory A.
影响因子：
7.8
作者：
Fairn, Gregory D.;Ogata, Koji;Grinstein, Sergio
通讯作者：
Grinstein, Sergio
影响因子：
9.8
作者：
Brown AC;Oddos S;Dobbie IM;Alakoskela JM;Parton RM;Eissmann P;Neil MA;Dunsby C;French PM;Davis I;Davis DM
通讯作者：
Davis DM
DOI：
10.1016/j.cub.2017.12.044
发表时间：
2018-02-19
期刊：
Current biology : CB
影响因子：
--
作者：
Carisey AF;Mace EM;Saeed MB;Davis DM;Orange JS
通讯作者：
Orange JS