通过Cdc42控制树突细胞内内细胞的发育控制
W S Garrett1, L M Chen, R Kroschewski
1Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Cell
|September 7, 2000
概括
树突细胞 (DCs) 通过调节内细胞分裂来控制抗原的吸收. 它们的内细胞能力在发育过程中受到Rho GTPase Cdc42的控制,影响免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 树突细胞 (DCs) 通过呈现抗原,在免疫反应中起着至关重要的作用.
- DC内细胞容量在发育上受到调节,不成熟的DC是内细胞的,成熟的DC是较少的.
- 罗家族GTPases是已知的细胞过程的调节者,包括内细胞分裂.
研究的目的:
- 调查Rho家族GTPases,特别是Cdc42在DC内细胞分裂的发育调节中的作用.
- 为了确定Cdc42活性如何影响不成熟和成熟DC的抗原吸收.
主要方法:
- 用毒素B治疗DCs以阻止Cdc42的功能.
- 使用主导阴性抑制剂抑制Cdc42的抑制.
- 在成熟的DC中使用构成性活性形式或核酸交换因子激活Cdc42.
- 在DC中测量内源Cdc42-GTP水平.
主要成果:
- 阻断Cdc42功能在不成熟的DC中取消了内细胞分裂.
- 在成熟的DC中激活Cdc42恢复了内细胞分裂.
- 激活的Cdc42 (Cdc42-GTP) 仅在未成熟的DC中检测到.
- DCs调节内源Cdc42-GTP的水平,影响它们的内细胞容量.
结论:
- 树突细胞内细胞分裂在发育上受到调节,至少部分是通过控制激活的Cdc42.
- 在免疫成熟过程中,Cdc42是调节DC内细胞活动的关键分子开关.
- 准Cdc42通路可以调节免疫相关疗法中的DC功能.
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