Developmental control of endocytosis in dendritic cells by Cdc42
Developmental control of endocytosis in dendritic cells by Cdc42
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DOI：
10.1016/s0092-8674(00)00038-6
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发表时间：
2000-08-04
期刊：
影响因子：
64.5
通讯作者：
Mellman, I
中科院分区：
文献类型：
--
作者：
Garrett, WS;Chen, LM;Mellman, I
树突状细胞（DC）通过控制其内吞能力来发育调节抗原摄取。未成熟DC主动内化抗原。然而，成熟DC的内吞作用较差，而是将抗原呈递给T细胞。我们已经发现，内吞下调反映了由Rho家族GTP酶，特别是Cdc 42控制的内吞活性的降低。通过毒素B处理或注射Cdc 42的显性负性抑制剂来阻断Cdc 42功能可消除未成熟DC中的内吞作用。在成熟DC中，注射组成型活性Cdc 42或微生物递送Cdc 42核苷酸交换因子重新激活内吞作用。DC调节内源性Cdc 42-GTP水平，活化的Cdc 42仅在未成熟细胞中可检测到。我们的结论是，发展中的DC调节内吞作用至少部分通过控制激活Cdc 42的水平。
Dendritic cells (DCs) developmentally regulate antigen uptake by controlling their endocytic capacity. Immature DCs actively internalize antigen. However, mature DCs are poorly endocytic, functioning instead to present antigens to T cells. We have found that endocytic downregulation reflects a decrease in endocytic activity controlled by Rho family GTPases, especially Cdc42. Blocking Cdc42 function by Toxin B treatment or injection of dominant-negative inhibitors of Cdc42 abrogates endocytosis in immature DCs. In mature DCs, injection of constitutively active Cdc42 or microbial delivery of a Cdc42 nucleotide exchange factor reactivates endocytosis. DCs regulate endogenous levels of Cdc42-GTP with activated Cdc42 detectable only in immature cells. We conclude that DCs developmentally regulate endocytosis at least in part by controlling levels of activated Cdc42.