脱颗粒
生物
免疫突触
细胞溶解
细胞毒性T细胞
GTP酶
鸟嘌呤核苷酸交换因子
细胞生物学
CD8型
自然杀伤细胞
溶解循环
拉布
免疫学
T细胞
免疫系统
遗传学
体外
病毒
受体
T细胞受体
作者
Michael J. Medlyn,E. Maeder,Claire Bradley,Prasad V. Phatarpekar,Hyoungjun Ham,Daniel D. Billadeau
摘要
Natural killer (NK) cells have the ability to lyse other cells through the release of lytic granules (LGs). This is in part mediated by the small GTPase Rab27a, which was first identified to play a crucial role in degranulation through the study of individuals harboring mutations in the gene encoding Rab27a. However, the guanine nucleotide exchange factor (GEF) regulating the activation of Rab27a in cytotoxic lymphocytes was unknown. Here, we show that knockout of MADD significantly decreased the levels of GTP-bound Rab27a in both resting and stimulated NK cells, and MADD-deficient NK cells and CD8+ T cells displayed severely reduced degranulation and cytolytic ability, similar to that seen with Rab27a deficiency. Although MADD colocalized with Rab27a on LGs and was enriched at the cytolytic synapse, the loss of MADD did not impact Rab27a association with LGs nor their recruitment to the cytolytic synapse. Together, our results demonstrate an important role for MADD in cytotoxic lymphocyte killing.
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