Scott K, Zuker C S
Howard Hughes Medical Institute, Department of Biology, University of California at San Diego, La Jolla 92093-0649, USA.
Nature. 1998 Oct 22;395(6704):805-8. doi: 10.1038/27448.
The subcellular compartmentalization of signalling molecules helps to ensure the selective activation of different signal-transduction cascades within a single cell. Although there are many examples of compartmentalized signalling molecules, there are few examples of entire signalling cascades being organized as distinct signalling complexes. In Drosophila photoreceptors, the InaD protein, which consists of five PDZ domains, functions as a multivalent adaptor that brings together several components of the phototransduction cascade into a macromolecular complex. Here we study single-photon responses in several photoreceptor mutant backgrounds, and show that the InaD macromolecular complex is the unit of signalling that underlies elementary responses. We show that the localized activity of this signalling unit promotes reliable single-photon responses as well as rapid activation and feedback regulation. Finally, we use genetic and electrophysiological tools to illustrate how the assembly of signalling molecules into a transduction complex limits signal amplification in vivo.
信号分子的亚细胞区室化有助于确保单个细胞内不同信号转导级联反应的选择性激活。尽管存在许多区室化信号分子的例子,但将整个信号级联反应组织成不同信号复合物的例子却很少。在果蝇光感受器中,由五个PDZ结构域组成的InaD蛋白作为一种多价衔接子,将光转导级联反应的几个组分聚集到一个大分子复合物中。在这里,我们研究了几种光感受器突变背景下的单光子反应,并表明InaD大分子复合物是构成基本反应基础的信号传导单位。我们表明,这个信号传导单位的局部活性促进了可靠的单光子反应以及快速激活和反馈调节。最后,我们使用遗传和电生理工具来说明信号分子组装成转导复合物如何在体内限制信号放大。