HOMOLOGY OF A 150K CYTOPLASMIC DYNEIN-ASSOCIATED POLYPEPTIDE WITH THE DROSOPHILA GENE GLUED

HOMOLOGY OF A 150K CYTOPLASMIC DYNEIN-ASSOCIATED POLYPEPTIDE WITH THE DROSOPHILA GENE GLUED
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DOI:
10.1038/351579a0
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发表时间:
1991-06-13
期刊:
影响因子:
64.8
通讯作者:
VALLEE, RB
VALLEE, RB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HOLZBAUR, ELF;HAMMARBACK, JA;VALLEE, RB

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胞质动力蛋白是一种微管激活的atp酶,它向微管1,2的负端产生力。它被认为负责轴突逆行运输和细胞器运动的其他方面2-6,并可能在有丝分裂染色体的极向运动中起作用7,8。细胞质动力蛋白是由两条催化重链和一些辅助亚基1,9,10组成的低聚物。我们现在报道了其中一个物种的互补DNA的克隆和测序,这是一个相对分子质量为150000 (M(r) 150K)的细胞质动力蛋白相关多肽。全长cDNA包含4.0千碱基的开放阅读框,预计编码M(r) 145K的多肽。它与果蝇基因glue的产物具有广泛的同源性,该基因编码M(r) 148k11的多肽。胶合突变是显性突变,在杂合子中具有多效性发育缺陷,在纯合子中具有胚胎致死表型。由于显性突变可能涉及正常蛋白-蛋白相互作用的破坏,glue突变应该提供细胞质动力蛋白在体内的作用模式的见解。
CYTOPLASMIC dynein is a microtubule-activated ATPase which produces force towards the minus ends of microtubules 1,2. It is thought to be responsible for retrograde axonal transport and other aspects of organelle motility 2-6 and may have a role in the poleward movement of mitotic chromosomes 7,8. Cytoplasmic dynein is an oligomeric complex of two catalytic heavy chains and a number of accessory subunits 1,9,10. We now report the cloning and sequencing of a complementary DNA for one of these species, a cytoplasmic dynein-associated polypeptide of relative molecular mass 150,000 (M(r) 150K). A full-length cDNA was found to contain an open reading frame of 4.0 kilobases, which is predicted to encode a polypeptide of M(r) 145K. It has extensive homology with the product of the Drosophila gene Glued, which encodes a polypeptide of M(r) 148K 11. The Glued mutation is dominant, with pleiotropic developmental defects in heterozygotes and an embryonic lethal phenotype in homozygotes. As dominant mutations may involve disruption of normal protein-protein interactions, the Glued mutation should provide insight into the mode of action of cytoplasmic dynein in vivo.