蛋白激酶Cθ（PKCθ）和Wiskott-Aldrich综合征蛋白（WASp）对免疫突触的对称性破坏和重新定位的相反作用。
Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse.
作者信息
Sims Tasha N, Soos Timothy J, Xenias Harry S, Dubin-Thaler Benjamin, Hofman Jake M, Waite Janelle C, Cameron Thomas O, Thomas V Kaye, Varma Rajat, Wiggins Chris H, Sheetz Michael P, Littman Dan R, Dustin Michael L
机构信息
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
出版信息
Cell. 2007 May 18;129(4):773-85. doi: 10.1016/j.cell.2007.03.037.
The immunological synapse (IS) is a junction between the T cell and antigen-presenting cell and is composed of supramolecular activation clusters (SMACs). No studies have been published on naive T cell IS dynamics. Here, we find that IS formation during antigen recognition comprises cycles of stable IS formation and autonomous naive T cell migration. The migration phase is driven by PKCtheta, which is localized to the F-actin-dependent peripheral (p)SMAC. PKCtheta(-/-) T cells formed hyperstable IS in vitro and in vivo and, like WT cells, displayed fast oscillations in the distal SMAC, but they showed reduced slow oscillations in pSMAC integrity. IS reformation is driven by the Wiscott Aldrich Syndrome protein (WASp). WASp(-/-) T cells displayed normal IS formation but were unable to reform IS after migration unless PKCtheta was inhibited. Thus, opposing effects of PKCtheta and WASp control IS stability through pSMAC symmetry breaking and reformation.
免疫突触（IS）是T细胞与抗原呈递细胞之间的连接结构，由超分子激活簇（SMACs）组成。目前尚未有关于初始T细胞IS动态变化的研究报道。在此，我们发现抗原识别过程中IS的形成包括稳定IS形成和初始T细胞自主迁移的循环。迁移阶段由蛋白激酶Cθ（PKCθ）驱动，PKCθ定位于依赖丝状肌动蛋白的外周（p）SMAC。PKCθ基因敲除（-/-）的T细胞在体外和体内形成超稳定的IS，并且与野生型（WT）细胞一样，在远端SMAC中表现出快速振荡，但它们在pSMAC完整性方面的缓慢振荡减少。IS的重新形成由威斯科特·奥尔德里奇综合征蛋白（WASp）驱动。WASp基因敲除（-/-）的T细胞表现出正常的IS形成，但迁移后除非抑制PKCθ，否则无法重新形成IS。因此，PKCθ和WASp的相反作用通过pSMAC的对称性破坏和重新形成来控制IS的稳定性。
Zotero 插件