Bowman A B, Patel-King R S, Benashski S E, McCaffery J M, Goldstein L S, King S M
Howard Hughes Medical Institute, Division of Cellular and Molecular Medicine, Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0683, USA.
J Cell Biol. 1999 Jul 12;146(1):165-80.
Eukaryotic organisms utilize microtubule-dependent motors of the kinesin and dynein superfamilies to generate intracellular movement. To identify new genes involved in the regulation of axonal transport in Drosophila melanogaster, we undertook a screen based upon the sluggish larval phenotype of known motor mutants. One of the mutants identified in this screen, roadblock (robl), exhibits diverse defects in intracellular transport including axonal transport and mitosis. These defects include intra-axonal accumulations of cargoes, severe axonal degeneration, and aberrant chromosome segregation. The gene identified by robl encodes a 97-amino acid polypeptide that is 57% identical (70% similar) to the 105-amino acid Chlamydomonas outer arm dynein-associated protein LC7, also reported here. Both robl and LC7 have homology to several other genes from fruit fly, nematode, and mammals, but not Saccharomyces cerevisiae. Furthermore, we demonstrate that members of this family of proteins are associated with both flagellar outer arm dynein and Drosophila and rat brain cytoplasmic dynein. We propose that roadblock/LC7 family members may modulate specific dynein functions.
真核生物利用驱动蛋白和动力蛋白超家族中依赖微管的马达来产生细胞内运动。为了鉴定参与果蝇轴突运输调控的新基因,我们基于已知马达突变体的幼虫行动迟缓表型进行了筛选。在此筛选中鉴定出的一个突变体,即路障(robl),在包括轴突运输和有丝分裂在内的细胞内运输中表现出多种缺陷。这些缺陷包括轴突内货物积累、严重的轴突退化和异常的染色体分离。由robl鉴定出的基因编码一种97个氨基酸的多肽,与本文也报道的105个氨基酸的衣藻外臂动力蛋白相关蛋白LC7有57%的同一性(70%的相似性)。robl和LC7与果蝇、线虫和哺乳动物的其他几个基因有同源性,但与酿酒酵母没有同源性。此外,我们证明了该蛋白家族的成员与鞭毛外臂动力蛋白以及果蝇和大鼠脑细胞质动力蛋白都有关联。我们提出路障/LC7家族成员可能调节特定的动力蛋白功能。