Centrosome polarization delivers secretory granules to the immunological synapse
Centrosome polarization delivers secretory granules to the immunological synapse
复制标题
DOI：
10.1038/nature05071
复制
发表时间：
2006-09-28
期刊：
影响因子：
64.8
通讯作者：
Griffiths, Gillian M.
中科院分区：
文献类型：
--
作者：
Stinchcombe, Jane C.;Majorovits, Endre;Griffiths, Gillian M.
细胞毒性T淋巴细胞(CTL)通过在CTL和靶细胞(1)之间形成的免疫突触释放特殊的分泌性溶酶体内容物--称为“裂解颗粒”--来破坏病毒感染和致瘤细胞。在与靶细胞接触时，CTL的微管组织中心朝着靶(2，3)极化，颗粒沿着微管以负端方向向极化的微管组织中心移动。然而，分泌的最后步骤仍不清楚。在这里，我们表明CTL不需要肌动蛋白或正端微管马达来分泌，而是中心体移动到免疫突触的中央超分子激活簇的质膜并与之接触。肌动蛋白和IQGAP1从突触中清除，颗粒直接输送到质膜。这些数据表明，CTL使用一种以前未见报道的机制将分泌颗粒运送到免疫突触，颗粒分泌由中心体运送到质膜控制。
Cytotoxic T lymphocytes (CTLs) destroy virally infected and tumorigenic cells by releasing the contents of specialized secretory lysosomes - termed 'lytic granules' - at the immunological synapse formed between the CTL and the target(1). On contact with the target cell, the microtubule organizing centre of the CTL polarizes towards the target(2,3) and granules move along microtubules in a minus-end direction towards the polarized microtubule organizing centre. However, the final steps of secretion have remained unclear. Here we show that CTLs do not require actin or plus-end microtubule motors for secretion, but instead the centrosome moves to and contacts the plasma membrane at the central supramolecular activation cluster of the immunological synapse. Actin and IQGAP1 are cleared away from the synapse, and granules are delivered directly to the plasma membrane. These data show that CTLs use a previously unreported mechanism for delivering secretory granules to the immunological synapse, with granule secretion controlled by centrosome delivery to the plasma membrane.