Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
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DOI：
10.1016/j.immuni.2009.05.009
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发表时间：
2009-07-17
期刊：
影响因子：
32.4
通讯作者：
Long, Eric O.
中科院分区：
文献类型：
--
作者：
Liu, Dongfang;Bryceson, Yenan T.;Meckel, Tobias;Vasiliver-Shamis, Gaia;Dustin, Michael L.;Long, Eric O.
细胞毒性淋巴细胞通过释放免疫突触分泌溶酶体的内容物杀死靶细胞。为了获得细胞毒性免疫突触的动力学和控制信息，我们对携带激活受体配体的脂质双分子层上的人类原代活的自然杀伤细胞进行了成像。有组织突触的形成依赖于β2整合素配体ICAM-1的存在。共激活受体2B4和NKG2D的配体分别分离到中央和外周区域。在脱颗粒过程中被排出的溶酶体蛋白LAMP-1聚集在一个空间稳定的大簇中，与膜内化位点重叠。溶酶体室室到达靠近中央积聚的LAMP-1的焦点处的质膜。固定细胞的成像显示，含穿孔素颗粒与细胞内腔室并列，在那里提取胞外分泌的LAMP-1。因此，细胞毒性免疫突触包括一个由整合素信号控制的双向囊泡交通的中心区域。
Cytotoxic lymphocytes kill target cells by releasing the content of secretory lysosomes at the immune synapse. To obtain information on the dynamics and control of cytotoxic immune synapses we imaged human primary, live natural killer cells on lipid bilayers carrying ligands of activation receptors. Formation of an organized synapse was dependent on the presence of the β2 integrin ligand ICAM-1. Ligands of co-activation receptors 2B4 and NKG2D segregated into central and peripheral regions, respectively. Lysosomal protein LAMP-1 that was exocytosed during degranulation accumulated in a large and spatially stable cluster, which overlapped with a site of membrane internalization. Lysosomal compartments reached the plasma membrane at focal points adjacent to centrally accumulated LAMP-1. Imaging of fixed cells revealed that perforin-containing granules were juxtaposed to an intracellular compartment where exocytosed LAMP-1 was retrieved. Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling.
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