Natural killer (NK) cells, cytolytic lymphocytes of the innate immune system, play a crucial role in the immune response against infection and cancer. NK cells kill target cells through exocytosis of lytic granules that contain cytotoxic proteins, such as perforin and granzymes. Formation of a functional immune synapse, i.e. the interface between the NK cell and its target cell enhances lysis through accumulation of polymerized F-actin at the NK cell synapse, leading to convergence of lytic granules to the microtubule organizing center (MTOC) and its subsequent polarization along microtubules to deliver the lytic granules to the synapse. In this review, we focus on the molecular mechanisms regulating the cellular processes that occur after the lytic granules are delivered to the cytotoxic synapse. We outline how - once near the synapse - the granules traverse the clearings created by F-actin remodeling to dock, tether and fuse with the plasma membrane in order to secrete their lytic content into the synaptic cleft through exocytosis. Further emphasis is given to the role of Ca2+ mobilization during degranulation and, whenever applicable, we compare these mechanisms in NK cells and cytotoxic T lymphocytes (CTLs) as adaptive immune system effectors.

中文翻译：

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涉及 NK 细胞溶细胞功能的质膜近端细胞步骤的分子调节。

自然杀伤 (NK) 细胞是先天免疫系统的溶细胞淋巴细胞，在针对感染和癌症的免疫反应中起着至关重要的作用。NK 细胞通过含有细胞毒性蛋白（如穿孔素和颗粒酶）的裂解颗粒的胞吐作用杀死靶细胞。功能性免疫突触的形成，即 NK 细胞与其靶细胞之间的界面，通过聚合 F-肌动蛋白在 NK 细胞突触处的积累增强裂解，导致裂解颗粒聚集到微管组织中心 (MTOC) 及其后续沿微管极化，将裂解颗粒输送到突触。在这篇综述中，我们关注调节细胞过程的分子机制，这些过程发生在裂解颗粒被递送到细胞毒性突触之后。我们概述了 - 一旦靠近突触 - 颗粒如何穿过 F-肌动蛋白重塑产生的空地，停靠、束缚并与质膜融合，以便通过胞吐作用将其裂解物分泌到突触间隙中。进一步强调了 Ca2+ 动员在脱颗粒过程中的作用，并且在适用时，我们将 NK 细胞和细胞毒性 T 淋巴细胞 (CTL) 中的这些机制作为适应性免疫系统效应器进行比较。