香叶基锗化
生物
法尼酰转移酶
细胞生物学
胸腺细胞
预酸化
免疫系统
T细胞
免疫学
生物化学
酶
作者
Xingrong Du,Hu Zeng,Shaofeng Liu,Cliff Guy,Yogesh Dhungana,Geoffrey Neale,Martin O. Bergö,Hongbo Chi
摘要
Thymocyte egress is a critical determinant of T cell homeostasis and adaptive immunity. Despite the roles of G protein–coupled receptors in thymocyte emigration, the downstream signaling mechanism remains poorly defined. Here, we report the discrete roles for the two branches of mevalonate metabolism–fueled protein prenylation pathway in thymocyte egress and immune homeostasis. The protein geranylgeranyltransferase Pggt1b is up-regulated in single-positive thymocytes, and loss of Pggt1b leads to marked defects in thymocyte egress and T cell lymphopenia in peripheral lymphoid organs in vivo. Mechanistically, Pggt1b bridges sphingosine-1-phosphate and chemokine-induced migratory signals with the activation of Cdc42 and Pak signaling and mevalonate-dependent thymocyte trafficking. In contrast, the farnesyltransferase Fntb, which mediates a biochemically similar process of protein farnesylation, is dispensable for thymocyte egress but contributes to peripheral T cell homeostasis. Collectively, our studies establish context-dependent effects of protein prenylation and unique roles of geranylgeranylation in thymic egress and highlight that the interplay between cellular metabolism and posttranslational modification underlies immune homeostasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI