Iijima Miho, Huang Yi Elaine, Devreotes Peter
Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Dev Cell. 2002 Oct;3(4):469-78. doi: 10.1016/s1534-5807(02)00292-7.
The ability to sense and respond to shallow gradients of extracellular signals is remarkably similar in Dictyostelium discoideum amoebae and mammalian leukocytes. Chemoattractant receptors and G proteins are fairly evenly distributed along the cell surface. Receptor occupancy generates local excitatory and global inhibitory processes that balance to control the chemotactic response. Uniform stimuli transiently recruit PI3Ks to, and release PTEN from, the plasma membrane, while gradients of chemoattractant cause the two enzymes to bind to the membrane at the front and back of the cell, respectively. Interference with PI3Ks alters chemotaxis, and disruption of PTEN broadens PI localization and actin polymerization in parallel. Thus, counteracting signals from the upstream elements of the pathway converge to regulate the key enzymes of PI metabolism, localize these lipids, and direct pseudopod formation.
盘基网柄菌变形虫和哺乳动物白细胞感知并响应细胞外信号浅梯度的能力非常相似。趋化因子受体和G蛋白在细胞表面分布相当均匀。受体占据会产生局部兴奋和全局抑制过程,二者相互平衡以控制趋化反应。均匀刺激会使PI3K瞬时募集到质膜并使PTEN从质膜释放,而趋化因子梯度会使这两种酶分别结合到细胞前端和后端的膜上。干扰PI3K会改变趋化作用,破坏PTEN则会同时拓宽磷脂酰肌醇(PI)定位和肌动蛋白聚合。因此,来自该信号通路上游元件的拮抗信号汇聚,以调节PI代谢的关键酶、定位这些脂质并指导伪足形成。