Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.
Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.
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DOI：
10.3389/fimmu.2022.871106
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
NK细胞介导的细胞毒性是我们免疫系统的一个关键要素，用于保护免受微生物感染和癌症。NK细胞通过向结合的靶细胞直接分泌细胞毒性分子来结合并消除感染的或癌性的细胞。在这篇综述中，我们总结了目前的理解NK细胞的细胞毒性的分子调控，重点是溶解颗粒的发展和脱粒过程。NK细胞合成凋亡诱导蛋白，并将其包装成称为裂解颗粒（LGs）的专门细胞器。在NK细胞活化后，LG通过动力蛋白依赖性运动沿沿着与微管组织中心会聚，最终极化至细胞毒性突触，随后与NK质膜融合。从LGs生物合成到脱粒，NK细胞利用几种策略来保护自己免受其自身细胞毒性分子的侵害。此外，使NK细胞能够执行连续杀伤的分子途径开始被阐明。这些在理解NK细胞细胞毒性背后的分子途径方面的进展不仅对改善目前基于NK细胞的抗癌疗法而且对支持发现其他治疗机会都很重要。
NK cell-mediated cytotoxicity is a critical element of our immune system required for protection from microbial infections and cancer. NK cells bind to and eliminate infected or cancerous cells via direct secretion of cytotoxic molecules toward the bound target cells. In this review, we summarize the current understanding of the molecular regulations of NK cell cytotoxicity, focusing on lytic granule development and degranulation processes. NK cells synthesize apoptosis-inducing proteins and package them into specialized organelles known as lytic granules (LGs). Upon activation of NK cells, LGs converge with the microtubule organizing center through dynein-dependent movement along microtubules, ultimately polarizing to the cytotoxic synapse where they subsequently fuse with the NK plasma membrane. From LGs biogenesis to degranulation, NK cells utilize several strategies to protect themselves from their own cytotoxic molecules. Additionally, molecular pathways that enable NK cells to perform serial killing are beginning to be elucidated. These advances in the understanding of the molecular pathways behind NK cell cytotoxicity will be important to not only improve current NK cell-based anti-cancer therapies but also to support the discovery of additional therapeutic opportunities.
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影响因子：
5.5
作者：
Ben-Shmuel A;Sabag B;Biber G;Barda-Saad M
通讯作者：
Barda-Saad M
影响因子：
56.9
作者：
Balint, S.;Muller, S.;Dustin, M. L.
通讯作者：
Dustin, M. L.
影响因子：
20.3
作者：
Bryceson, Yenan T.;Rudd, Eva;Ljunggren, Hans-Gustaf
通讯作者：
Ljunggren, Hans-Gustaf
影响因子：
4.4
作者：
Bin，Na-Ryum;Ma，Ke;Sugita，Shuzo
通讯作者：
Sugita，Shuzo
影响因子：
24.1
作者：
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通讯作者：
Watzl, Carsten