不同的信号和细胞骨架组合调节中性粒细胞的自我组织极性
Jingsong Xu1, Fei Wang, Alexandra Van Keymeulen
1Department of Cellular and Molecular Pharmacology and The Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
细胞极化依赖于三元基G蛋白的对立信号. 这些信号涉及Rac和Rho GTPases,控制着actin动力学,使细胞能够在对化学吸引剂的反应中进行定向的细胞运动.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 不同化的HL-60细胞和中性友白细胞在对化疗吸引剂的反应中表现出极化形态.
- 这种两极分化涉及细胞前边和后边的独特的基于actin的结构.
研究的目的:
- 阐明基因吸引剂诱导的细胞极性背后的分子机制.
- 确定特定的信号通路和蛋白质,参与建立和维持细胞极性.
主要方法:
- 利用药理抑制剂,毒素和突变蛋白来剖析信号通路.
- 研究了三元基G蛋白 (Gi,G12,G13),小GTPases (Rac,Rho) 和它们的下游效应者的作用.
主要成果:
- 证明细胞极性是由不同的G蛋白调解的对立的"前面"和"后面"信号驱动的.
- 基信号通过3'-氨基醇脂质 (PI3Ps),激活的Rac和F-actin来促进"正面性".
- G12/G13信号通过Rho激活,Rho依赖性激酶和肌酸酶II诱导"后退".
结论:
- "前端"和"后端"路径之间的功能不相容会产生不同的actin域,增强前端敏感性.
- 这种机制解释了中性粒细胞在均的化学吸引剂度和对梯度逆转的U转反应中的两极分化.
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