Cytoplasmic dynein, the dynactin complex, and kinesin are interdependent and essential for fast axonal transport
Cytoplasmic dynein, the dynactin complex, and kinesin are interdependent and essential for fast axonal transport
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DOI：
10.1091/mbc.10.11.3717
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发表时间：
1999-11-01
影响因子：
3.3
通讯作者：
Saxton, WM
中科院分区：
文献类型：
--
作者：
Martin, M;Iyadurai, SJ;Saxton, WM
在轴突中，细胞器沿着沿着微管远离（顺行）和朝向（逆行）细胞体移动。以往的研究提供了令人信服的证据，传统的驱动蛋白是一个主要的马达顺行快速轴突运输。这是合理的预期，细胞质动力蛋白是一个快速逆行马达，但相对较少的测试动力蛋白功能的完整生物体的神经元的报道。在挤压轴浆中，驱动蛋白或动力蛋白复合物（动力蛋白激活剂）的抗体破坏抑制逆行和顺行运输。我们已经测试了细胞质动力蛋白重链（cDhc64C）和p150（Glued）（Glued）组件的dynactin复杂的功能与使用遗传技术在果蝇。cDhc64C和Glued突变在两个方向上破坏快速细胞器运输。突变体的表型，幼虫后部麻痹和轴突slogs充满逆行和顺行货物，是类似的驱动蛋白突变所造成的。为什么单向运动系统的特定中断会引起双向运动。缺陷？未检测到驱动蛋白与动力蛋白重链和p150（Glued）的直接蛋白质相互作用。然而，强烈的显性遗传之间的相互作用，驱动蛋白，动力蛋白，动力蛋白复合物突变轴突运输观察。驱动蛋白与Glued或cDhc64C突变之间的遗传相互作用强于Glued和cDhc64C突变本身之间的相互作用。共享的双向中断表型和显性遗传相互作用表明，细胞质动力蛋白，动力蛋白复合物，和传统的驱动蛋白是相互依赖的快速轴突运输。
In axons, organelles move away from (anterograde) and toward (retrograde) the cell body along microtubules. Previous studies have provided compelling evidence that conventional kinesin is a major motor for anterograde fast axonal transport. It is reasonable to expect that cytoplasmic dynein is a fast retrograde motor, but relatively few tests of dynein function have been reported with neurons of intact organisms. In extruded axoplasm, antibody disruption of kinesin or the dynactin complex (a dynein activator) inhibits both retrograde and anterograde transport. We have tested the functions of the cytoplasmic dynein heavy chain (cDhc64C) and the p150(Glued) (Glued) component of the dynactin complex with the use of genetic techniques in Drosophila. cDhc64C and Glued mutations disrupt fast organelle transport in both directions. The mutant phenotypes, larval posterior paralysis and axonal swellings filled with retrograde and anterograde cargoes, were similar to those caused by kinesin mutations. Why do specific disruptions of unidirectional motor systems cause bidirectional. defects? Direct protein interactions of kinesin with dynein heavy chain and p150(Glued) were not detected. However, strong dominant genetic interactions between kinesin, dynein, and dynactin complex mutations in axonal transport were observed. The genetic interactions between kinesin and either Glued or cDhc64C mutations were stronger than those between Glued and cDhc64C mutations themselves. The shared bidirectional disruption phenotypes and the dominant genetic interactions demonstrate that cytoplasmic dynein, the dynactin complex, and conventional kinesin are interdependent in fast axonal transport.