Department of Biology, University of Toronto Mississauga, Mississauga, Canada.
Peptides. 2012 Mar;34(1):145-9. doi: 10.1016/j.peptides.2011.12.014. Epub 2012 Jan 3.
A synthetic EGF-like (EGFL) peptide (DdEGFL1), equivalent to the first EGFL domain in the extracellular matrix protein CyrA, has previously been shown to enhance random cell motility and cAMP-mediated chemotaxis in Dictyostelium discoideum. However the role of DdEGFL1 as a potential chemoattractant had not been addressed. In this study, a micropipette assay and an under-agarose migration assay showed that DdEGFL1 is not a chemoattractant for Dictyostelium cells. A radial bioassay was used to show that DdEGFL1 does not significantly enhance folate-mediated chemotaxis in contrast to its chemokinetic effect during chemotaxis toward cAMP. However, DdEGFL1 was able to rescue chemotaxis toward folate when the pathway was inhibited by pharmacological agents that inhibit known components of the signaling cascade (e.g. phosphatidylinositol 3-kinase, phospholipase A2, tyrosine kinases, and calmodulin). These data suggest that DdEGFL1 may activate a novel motility pathway that when coupled with folic acid receptor activation, can maintain the normal migratory response to folic acid in vegetative cells. Together, this data provides new insight into the function of EGFL repeats during Dictyostelium chemotaxis and the existence of a novel motility pathway regulated by EGFL peptides and/or repeats in this model organism.
一种合成的表皮生长因子样（EGFL）肽（DdEGFL1），相当于细胞外基质蛋白 CyrA 中的第一个 EGFL 结构域，先前已被证明可增强盘基网柄菌中的随机细胞运动和 cAMP 介导向化运动。然而，DdEGFL1 作为潜在趋化剂的作用尚未得到解决。在这项研究中，微量移液管测定和琼脂下迁移测定表明 DdEGFL1 不是盘基网柄菌细胞的趋化剂。放射状生物测定表明，DdEGFL1 与 cAMP 介导向化运动中的趋动作用相比，并没有显著增强叶酸介导的趋化运动。然而，当通过抑制已知信号级联成分（例如磷脂酰肌醇 3-激酶、磷脂酶 A2、酪氨酸激酶和钙调蛋白）的药理学制剂抑制已知信号级联成分时，DdEGFL1 能够挽救叶酸介导的趋化运动。这些数据表明，DdEGFL1 可能激活一种新的运动途径，当与叶酸受体激活偶联时，可维持营养细胞对叶酸的正常迁移反应。总的来说，这些数据为 EGFL 重复在盘基网柄菌趋化作用中的功能以及 EGFL 肽和/或重复在该模式生物中调节的新型运动途径的存在提供了新的见解。
