Jalink K, Moolenaar W H, Van Duijn B
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1857-61. doi: 10.1073/pnas.90.5.1857.
The naturally occurring phospholipid lysophosphatidic acid (LPA) can induce a number of physiological responses in vertebrate cells, including platelet aggregation, smooth muscle contraction, and fibroblast proliferation. LPA is thought to activate a specific G-protein-coupled receptor, thereby triggering classic second messenger pathways such as stimulation of phospholipase C and inhibition of adenylate cyclase. Here we report that 1-oleoyl-LPA, at submicromolar concentrations, evokes a chemotactic response in amoebae of the cellular slime mold Dictyostelium discoideum. LPA-induced chemotaxis is specific in that other lysophospholipids, phosphatidic acid, and monoacylglycerol have no effect. We show that the response to LPA is not secondary to the accumulation of extracellular cAMP, a well-established chemoattractant for nutrient-starved D. discoideum. Compared with cAMP-induced chemotaxis, LPA-induced chemotaxis has a somewhat lower efficiency and is not accompanied by the characteristic cellular elongation and orientation along the gradient. These results indicate that LPA has a previously unsuspected role as a chemoattractant for D. discoideum and imply that its biological function as a "first messenger" is not restricted to vertebrate cells.
天然存在的磷脂溶血磷脂酸(LPA)可在脊椎动物细胞中诱导多种生理反应,包括血小板聚集、平滑肌收缩和成纤维细胞增殖。LPA被认为可激活一种特定的G蛋白偶联受体,从而触发经典的第二信使途径,如刺激磷脂酶C和抑制腺苷酸环化酶。在此我们报告,亚微摩尔浓度的1-油酰-LPA可在细胞黏菌盘基网柄菌的变形虫中引发趋化反应。LPA诱导的趋化作用具有特异性,因为其他溶血磷脂、磷脂酸和单酰甘油均无作用。我们表明,对LPA的反应并非继发于细胞外cAMP的积累,cAMP是营养饥饿的盘基网柄菌公认的趋化因子。与cAMP诱导的趋化作用相比,LPA诱导的趋化作用效率略低,且不伴有沿梯度的特征性细胞伸长和定向。这些结果表明,LPA作为盘基网柄菌的趋化因子具有此前未被怀疑的作用,并暗示其作为“第一信使”的生物学功能并不局限于脊椎动物细胞。