Caterina M J, Devreotes P N
Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205.
FASEB J. 1991 Dec;5(15):3078-85.
Many cells display directed migration toward specific compounds. The best-studied eukaryotic models of chemotaxis are polymorphonuclear leukocytes, which respond to formylated peptides and Dictyostelium amoebas, which respond to extracellular cAMP. In both cell types, chemoattractants bind to surface receptors that contain seven transmembrane domains and interact with G proteins. Some cells, such as fibroblasts, undergo chemotaxis toward compounds whose receptors lack this motif and transmit their signals by other mechanisms. The cytosolic changes elicited by chemoattractants include increased levels of cAMP, cGMP, inositol phosphates, and calcium. These changes are correlated with actin polymerization and other cytoskeletal events that result in preferential extension of pseudopods toward the chemoattractant. Dictyostelium cell lines in which specific genes have been disrupted have demonstrated the necessity of a cAMP receptor (cAR1) and a G protein alpha-subunit (G alpha 2) for responsiveness to cAMP. Other proteins, such as myosin heavy chain and several actin binding proteins, are dispensible although their absence does affect the details of chemotaxis. The disruption of other relevant genes and the genetic reconstitution of chemotaxis in cells lacking crucial proteins should reveal many clues about this complicated and fascinating process.
许多细胞会朝着特定化合物进行定向迁移。研究得最为透彻的真核生物趋化模型是多形核白细胞，它对甲酰化肽作出反应；还有盘基网柄菌变形虫，它对细胞外的环磷酸腺苷（cAMP）作出反应。在这两种细胞类型中，趋化因子都与含有七个跨膜结构域并与G蛋白相互作用的表面受体结合。有些细胞，比如成纤维细胞，会朝着其受体缺乏该基序并通过其他机制传递信号的化合物进行趋化。趋化因子引发的胞质变化包括环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）、肌醇磷酸和钙的水平升高。这些变化与肌动蛋白聚合及其他细胞骨架事件相关，这些事件导致伪足朝着趋化因子优先延伸。已破坏特定基因的盘基网柄菌细胞系表明，对cAMP作出反应需要一个cAMP受体（cAR1）和一个G蛋白α亚基（Gα2）。其他蛋白质，如肌球蛋白重链和几种肌动蛋白结合蛋白，虽然它们的缺失确实会影响趋化的细节，但并非必不可少。破坏其他相关基因以及对缺乏关键蛋白质的细胞进行趋化的基因重组，应该会揭示出许多有关这个复杂而迷人过程的线索。
