Tsunoda S, Sierralta J, Sun Y, Bodner R, Suzuki E, Becker A, Socolich M, Zuker C S
Howard Hughes Medical Institute, and Department of Biology, University of California at San Diego, La Jolla 92093-0649, USA.
Nature. 1997 Jul 17;388(6639):243-9. doi: 10.1038/40805.
How are signalling molecules organized into different pathways within the same cell? In Drosophila, the inaD gene encodes a protein consisting of five PDZ domains which serves as a scaffold to assemble different components of the phototransduction cascade, including the principal light-activated ion channels, the effector phospholipase C-beta and protein kinase C. Null inaD mutants have a dramatically reorganized subcellular distribution of signalling molecules, and a total loss of transduction complexes. Also, mutants defective in a single PDZ domain produce signalling complexes that lack the target protein and display corresponding defects in their physiology. A picture emerges of a highly organized unit of signalling, a 'transduclisome', with PDZ domains functioning as key elements in the organization of transduction complexes in vivo.
信号分子是如何在同一细胞内组织成不同的信号通路的？在果蝇中，inaD基因编码一种由五个PDZ结构域组成的蛋白质，该蛋白质作为一种支架，组装光转导级联反应的不同组分，包括主要的光激活离子通道、效应器磷脂酶C-β和蛋白激酶C。inaD基因敲除突变体的信号分子亚细胞分布发生了显著重组，并且转导复合物完全丧失。此外，单个PDZ结构域有缺陷的突变体产生的信号复合物缺少靶蛋白，并在其生理功能上表现出相应的缺陷。由此浮现出一幅高度组织化的信号单元“转导体”的图景，其中PDZ结构域在体内转导复合物的组织中起着关键作用。
