Myosin IIA is required for cytolytic granule exocytosis in human NK cells.

Myosin IIA is required for cytolytic granule exocytosis in human NK cells.
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DOI:
10.1084/jem.20071143
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发表时间:
2007-10-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Strominger JL
Strominger JL
中科院分区:
其他
文献类型:
--
作者:
Andzelm MM;Chen X;Krzewski K;Orange JS;Strominger JL

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自然杀伤细胞(NK)细胞毒作用涉及在效应器和靶细胞之间形成一种激活的免疫突触(IS),通过该突触,裂解颗粒中的颗粒酶和穿孔素通过胞吐作用被运送到靶细胞。用Blebbistatin或ML-9抑制人NK细胞中的非肌肉肌球蛋白II既不会损害效应-靶细胞的结合,也不会损害成熟的激活NK细胞的形成(NKIS;肌动蛋白环的形成和微管组织中心和溶细胞颗粒向环中心的极化)。然而,溶解颗粒的膜融合、颗粒酶分泌和NK细胞杀伤作用都被有效地阻断。RNA干扰对肌球蛋白IIA重链的特异性敲除会损害细胞毒性、溶解颗粒的膜融合和颗粒酶的分泌。因此,肌球蛋白IIA是NKIS形成和颗粒胞吐之间的关键步骤。
Natural killer (NK) cell cytotoxicity involves the formation of an activating immunological synapse (IS) between the effector and target cell through which granzymes and perforin contained in lytic granules are delivered to the target cell via exocytosis. Inhibition of nonmuscle myosin II in human NK cells with blebbistatin or ML-9 impaired neither effector–target cell conjugation nor formation of a mature activating NK cell IS (NKIS; formation of an actin ring and polarization of the microtubule-organizing center and cytolytic granules to the center of the ring). However, membrane fusion of lytic granules, granzyme secretion, and NK cell cytotoxicity were all effectively blocked. Specific knockdown of the myosin IIA heavy chain by RNA interference impaired cytotoxicity, membrane fusion of lytic granules, and granzyme secretion. Thus, myosin IIA is required for a critical step between NKIS formation and granule exocytosis.
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