APLIP1, a Kinesin binding JIP-1/JNK scaffold protein, influences the axonal transport of both vesicles and mitochondria in Drosophila
APLIP1, a Kinesin binding JIP-1/JNK scaffold protein, influences the axonal transport of both vesicles and mitochondria in Drosophila
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DOI：
10.1016/j.cub.2005.10.047
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发表时间：
2005-12-06
期刊：
影响因子：
9.2
通讯作者：
Saxton, WM
中科院分区：
文献类型：
--
作者：
Horiuchi, D;Barkus, RV;Saxton, WM
在驱动蛋白重链（Khc）相互作用蛋白的遗传筛选中，我们鉴定了APLIP 1，一种神经元表达的JIP-1（JNK支架蛋白）果蝇同源物[1]。已经提出JIP-1及其同源物作为驱动蛋白-1（其为正末端定向微管马达）与培养的神经元的轴突中的某些顺行囊泡之间的物理连接物[2]。Aplip 1的突变引起幼虫麻痹，轴突serpent，并降低水平的顺行和逆行囊泡运输，类似于驱动蛋白-1抑制的影响。相反，Aplip 1突变仅导致线粒体逆行转运减少，表明负端微管运动细胞质动力蛋白的抑制[3]。与动力蛋白缺陷一致，Aplip 1和动力蛋白重链（Dhc 64 C）中的杂合突变组合产生合成轴突运输表型。因此，APLIP 1可能是驱动蛋白-1和动力蛋白的马达-货物连接复合物的重要组成部分。然而，同样值得考虑的是，APLIP 1及其相关的JNK信号蛋白可以作为一个重要的信号模块，用于调节两个相反的马达的运输。
In a genetic screen for Kinesin heavy chain (Khc)interacting proteins, we identified APLIP1, a neuronally expressed Drosophila homolog of JIP-1, a JNK scaffolding protein [1]. JIP-1 and its homologs have been proposed to act as physical linkers between kinesin-1, which is a plus-end-directed microtubule motor, and certain anterograde vesicles in the axons of cultured neurons [2]. Mutation of Aplip1 caused larval paralysis, axonal swellings, and reduced levels of both anterograde and retrograde vesicle transport, similar to the effects of kinesin-1 inhibition. In contrast, Aplip1 mutation caused a decrease only in retrograde transport of mitochondria, suggesting inhibition of the minus-end microtubule motor cytoplasmic dynein [3]. Consistent with dynein defects, combining heterozygous mutations in Aplip1 and Dynein heavy chain (Dhc64C) generated synthetic axonal transport phenotypes. Thus, APLIP1 may be an important part of motor-cargo linkage complexes for both kinesin-1 and dynein. However, it is also worth considering that APLIP1 and its associated JNK signaling proteins could serve as an important signaling module for regulating transport by the two opposing motors.