不可裂解的踝蛋白可挽救免疫衔接蛋白SKAP1缺陷的T细胞在T细胞结合方面的缺陷。
Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1.
作者信息
Lim Daina, Lu Yuning, Rudd Christopher E
机构信息
Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK; Cambridge Institute of Medical Research, Hills Road, CB2 OXY Cambridge, UK.
Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK; Cambridge Institute of Medical Research, Hills Road, CB2 OXY Cambridge, UK.
出版信息
Immunol Lett. 2016 Apr;172:40-6. doi: 10.1016/j.imlet.2016.02.004. Epub 2016 Feb 19.
While the cytoskeletal protein talin binds to the β-chain of LFA-1, the immune cell adaptor SKAP1 (SKAP-55) binds to the α-chain of the same integrin via RapL. Whereas calpain protease cleavage of talin is important for LFA-1 activation, it has been unclear whether SKAP1 can alter the function of talin or its associated adaptor RIAM in T-cells. In this paper, we report that Skap1-/- T-cells showed a reduction in the translocation of talin and RIAM to the contact interface of T-cells with antigenic beads or dendritic cells (DCs) presenting OVA peptide to OT-1 T-cells. In addition, Skap1-/- T-cells show an altered pattern of talin cleavage, while the expression of a cleavage resistant form of talin (L432G) restored the impaired adhesion of OT1 transgenic Skap1-/- T-cells with DCs. SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation.
细胞骨架蛋白踝蛋白可与淋巴细胞功能相关抗原-1（LFA-1）的β链结合，而免疫细胞衔接蛋白SKAP1（SKAP-55）则通过RapL与同一整合素的α链结合。虽然钙蛋白酶对踝蛋白的切割对LFA-1的激活很重要，但尚不清楚SKAP1是否能改变T细胞中踝蛋白或其相关衔接蛋白RIAM的功能。在本文中，我们报道Skap1基因敲除的T细胞中，踝蛋白和RIAM向T细胞与抗原珠或向OT-1 T细胞呈递卵清蛋白（OVA）肽的树突状细胞（DC）接触界面的转位减少。此外，Skap1基因敲除的T细胞显示出踝蛋白切割模式的改变，而一种抗切割形式的踝蛋白（L432G）的表达恢复了OT1转基因Skap1基因敲除的T细胞与DC受损的黏附。因此，SKAP1可以影响T细胞中踝蛋白的功能，而这是最佳T细胞/DC结合所必需的。
Zotero 插件