Interorganelle Tethering to Endocytic Organelles Determines Directional Cytokine Transport in CD4+ T Cells

被引:1
作者
Zhou, Yan [1 ]
Zhao, Renping [1 ]
Schwarz, Eva C. [1 ]
Akbar, Rahmad [2 ]
Kaba, Mayis [3 ]
Pattu, Varsha [4 ]
Helms, Volkhard [2 ]
Rieger, Heiko [5 ]
Nunes-Hasler, Paula [3 ,6 ]
Bin Qu [1 ,7 ]
机构
[1] Saarland Univ, Ctr Integrat Physiol & Mol Med, Sch Med, Dept Biophys, Bldg 48, D-66421 Homburg, Germany
[2] Saarland Univ, Ctr Bioinformat, D-66123 Saarbrucken, Germany
[3] Univ Geneva, Univ Med Ctr, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland
[4] Saarland Univ, Ctr Integrat Physiol & Mol Med, Sch Med, Dept Physiol, D-66421 Homburg, Germany
[5] Saarland Univ, Dept Theoret Phys, D-66123 Saarbrucken, Germany
[6] Univ Geneva, Univ Med Ctr, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland
[7] Leibniz Inst New Mat, D-66123 Saarbrucken, Germany
基金
瑞士国家科学基金会;
关键词
IMMUNOLOGICAL SYNAPSE; SNARE COMPLEX; CONTACT SITES; MITOCHONDRIA; HELPER; PREDICTION; PATHWAYS; PROTEINS; VACUOLES; ADAPTER;
D O I
10.4049/jimmunol.2000195
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Delivery of vesicles to their desired destinations plays a central role in maintaining proper cell functionality. In certain scenarios, depending on loaded cargos, the vesicles have spatially distinct destinations. For example, in T cells, some cytokines (e.g., IL-2) are polarized to the T cell-target cell interface, whereas the other cytokines are delivered multidirectionally (e.g., TNF-alpha). In this study, we show that in primary human CD4(+) T cells, both TNF-alpha(+) and IL-2(+) vesicles can tether with endocytic organelles (lysosomes/late endosomes) by forming membrane contact sites. Tethered cytokine-containing vesicle (CytV)-endocytic organelle pairs are released sequentially. Only endocytic organelle-tethered CytVs are preferentially transported to their desired destination. Mathematical models suggest that endocytic organelle tethering could regulate the direction of cytokine transport by selectively attaching different microtubule motor proteins (such as kinesin and dynein) to the corresponding CytVs. These findings establish the previously unknown interorganelle tethering to endocytic organelles as a universal solution for directional cytokine transport in CD4(+) T cells. Modulating tethering to endocytic organelles can, therefore, coordinately control directionally distinct cytokine transport.
引用
收藏
页码:2988 / +
页数:19
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