Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides
Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides
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DOI：
10.1091/mbc.e07-03-0261
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Saxton, William M.
中科院分区：
文献类型：
--
作者：
Barkus, Rosemarie V.;Klyachko, Olga;Saxton, William M.
对果蝇眼睛发育所需基因的筛选发现了一种与UNC-104/Kif1相关的驱动蛋白-3微管马达。对突变体的分析表明，果蝇Unc-104具有不同于经典的顺行轴突运动蛋白激酶1的神经元功能。特别是，unc-104突变不会引起运动蛋白-1 （Khc）突变所特有的远端麻痹和局灶性轴突肿胀。然而，像Khc突变一样，unc-104突变引起运动神经元末端萎缩。绿色荧光蛋白标记的细胞器在运动轴突中的分布和转运行为表明，Unc-104对充满神经肽的囊泡的顺行快速转运起主要作用，同时也对携带synaptotagin的囊泡的顺行转运起作用，而对线粒体的顺行转运起作用很小或没有作用，线粒体主要由Khc转运。值得注意的是，unc-104突变抑制神经分泌囊泡的逆行运行，而不影响其他两个细胞器。这表明Unc-104，一个顺行动力蛋白亚家族的成员，有助于细胞器特异性动力蛋白驱动的逆行运输机制。
A screen for genes required in Drosophila eye development identified an UNC-104/Kif1 related kinesin-3 microtubule motor. Analysis of mutants suggested that Drosophila Unc-104 has neuronal functions that are distinct from those of the classic anterograde axonal motor, kinesin-1. In particular, unc-104 mutations did not cause the distal paralysis and focal axonal swellings characteristic of kinesin-1 (Khc) mutations. However, like Khc mutations, unc-104 mutations caused motoneuron terminal atrophy. The distributions and transport behaviors of green fluorescent protein-tagged organelles in motor axons indicate that Unc-104 is a major contributor to the anterograde fast transport of neuropeptide-filled vesicles, that it also contributes to anterograde transport of synaptotagmin-bearing vesicles, and that it contributes little or nothing to anterograde transport of mitochondria, which are transported primarily by Khc. Remarkably, unc-104 mutations inhibited retrograde runs by neurosecretory vesicles but not by the other two organelles. This suggests that Unc-104, a member of an anterograde kinesin subfamily, contributes to an organelle-specific dynein-driven retrograde transport mechanism.