Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse

被引:249
作者
Finetti, Francesca [1 ]
Paccani, Silvia Rossi [1 ]
Riparbelli, Maria Giovanna [1 ]
Giacomello, Emiliana
Perinetti, Giuseppe [2 ]
Pazour, Gregory J. [3 ]
Rosenbaum, Joel L. [4 ]
Baldari, Cosima T. [1 ]
机构
[1] Univ Siena, Dept Evolutionary Biol, I-53100 Siena, Italy
[2] Univ Trieste, Dept Biomed, I-34138 Trieste, Italy
[3] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA
[4] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
T-CELL-ACTIVATION; ANTIGEN; RECEPTOR; CILIUM; TCR; INTERNALIZATION; MECHANISMS; PROTEIN; IFT20;
D O I
10.1038/ncb1977
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Most eukaryotic cells have a primary cilium which functions as a sensory organelle(1). Cilia are assembled by intraflagellar transport (IFT), a process mediated by multimeric IFT particles and molecular motors(2). Here we show that lymphoid and myeloid cells, which lack primary cilia, express IFT proteins. IFT20, an IFT component essential for ciliary assembly(3,4), was found to colocalize with both the microtubule organizing centre (MTOC) and Golgi and post-Golgi compartments in T-lymphocytes. In antigen-specific conjugates, IFT20 translocated to the immune synapse. IFT20 knockdown resulted in impaired T-cell receptor/CD3 (TCR/CD3) clustering and signalling at the immune synapse, due to defective polarized recycling. Moreover, IFT20 was required for the inducible assembly of a complex with other IFT components (IFT57 and IFT88) and the TCR. The results identify IFT20 as a new regulator of immune synapse assembly in T cells and provide the first evidence to implicate IFT in membrane trafficking in cells lacking primary cilia, thereby introducing a new perspective on IFT function beyond its role in ciliogenesis.
引用
收藏
页码:1332 / U163
页数:17
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