Dormann D, Kim J Y, Devreotes P N, Weijer C J
School of Life Sciences, Division of Cell and Developmental Biology, University of Dundee, Wellcome Trust Biocentre, Dow Street, Dundee, DD1 5EH, UK.
J Cell Sci. 2001 Jul;114(Pt 13):2513-23. doi: 10.1242/jcs.114.13.2513.
Serpentine G-protein-coupled cAMP receptors are key components in the detection and relay of the extracellular cAMP waves that control chemotactic cell movement during Dictyostelium development. During development the cells sequentially express four closely related cAMP receptors of decreasing affinity. In this study, we investigated the effect of cAMP receptor type and affinity on the dynamics of cell-cell signalling in vivo, by measuring the dynamics of wave initiation and propagation in a variety of cAMP receptor mutants. We found that receptor affinity controls the frequency of wave initiation, but it does not determine wave propagation velocity, thus resulting in dramatic changes in wave geometry. In the limiting case, the affinity of the receptor is so low that waves can still be initiated but no stable centres form - thus, the cells cannot aggregate. In mounds, expression of low affinity receptors results in slow concentric waves instead of the normally observed multi-armed spiral waves. Under these conditions there is no rotational cell movement and the hemispherical mounds cannot transform into slugs. These results highlight the importance of receptor number and affinity in the proper control of cell-cell signalling dynamics required for the successful completion of development.
蛇形G蛋白偶联cAMP受体是检测和传递细胞外cAMP波的关键成分，这些波在盘基网柄菌发育过程中控制趋化性细胞运动。在发育过程中，细胞依次表达四种亲和力递减的密切相关的cAMP受体。在本研究中，我们通过测量各种cAMP受体突变体中波起始和传播的动力学，研究了cAMP受体类型和亲和力对体内细胞间信号传导动力学的影响。我们发现受体亲和力控制波起始的频率，但不决定波的传播速度，从而导致波的几何形状发生显著变化。在极限情况下，受体的亲和力非常低，以至于波仍然可以起始，但不会形成稳定的中心——因此，细胞无法聚集。在丘状体中，低亲和力受体的表达导致缓慢的同心波，而不是通常观察到的多臂螺旋波。在这些条件下，没有细胞的旋转运动，半球形丘状体也无法转化为蛞蝓体。这些结果突出了受体数量和亲和力在成功完成发育所需的细胞间信号传导动力学的适当控制中的重要性。
