Mizuno Katsutoshi, Dymek Erin E, Smith Elizabeth F
Center for Developmental Biology, RIKEN 2-2-3 Minatojima-minamimachi, Chuou-ku, Kobe, Japan.
Department of Biological Sciences, Class of 1978 Life Sciences Center Dartmouth College, Hanover, New Hampshire.
Cytoskeleton (Hoboken). 2016 Dec;73(12):703-711. doi: 10.1002/cm.21340. Epub 2016 Nov 8.
The complex waveforms characteristic of motile eukaryotic cilia and flagella are produced by the temporally and spatially regulated action of multiple dynein subforms generating sliding between subsets of axonemal microtubules. Multiple protein complexes have been identified that are associated with the doublet microtubules and that mediate regulatory signals between key axonemal structures, such as the radial spokes and central apparatus, and the dynein arm motors; these complexes include the N-DRC, MIA, and CSC complexes. Previous studies have shown that PACRG (parkin co-regulated gene) forms a complex that is anchored to the axonemal doublet microtubules. Loss of PACRG causes defects in ciliary motility and cilia related diseases. Here, we use an in vitro microtubule sliding assay to demonstrate that PACRG and its interactors are part of a signaling pathway that includes the central apparatus, radial spokes and specific inner dynein arm subforms to control dynein-driven microtubule sliding. Using a biochemical approach, our studies also indicate that PACRG interacts with the radial spokes. © 2016 Wiley Periodicals, Inc.
运动性真核生物纤毛和鞭毛所特有的复杂波形是由多种动力蛋白亚型在时间和空间上受调控的作用产生的,这些动力蛋白亚型在轴丝微管亚群之间产生滑动。已经鉴定出多种与双联微管相关的蛋白质复合物,它们介导关键轴丝结构(如放射辐条和中央微管)与动力蛋白臂马达之间的调节信号;这些复合物包括N-DRC、MIA和CSC复合物。先前的研究表明,PACRG(帕金森病共调控基因)形成一种复合物,该复合物锚定在轴丝双联微管上。PACRG的缺失会导致纤毛运动缺陷和与纤毛相关的疾病。在这里,我们使用体外微管滑动试验来证明PACRG及其相互作用蛋白是信号通路的一部分,该信号通路包括中央微管、放射辐条和特定的内侧动力蛋白臂亚型,以控制动力蛋白驱动的微管滑动。通过生化方法,我们的研究还表明PACRG与放射辐条相互作用。©2016威利期刊公司