A determinant for directionality of organelle transport in Drosophila embryos

A determinant for directionality of organelle transport in Drosophila embryos
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DOI:
10.1016/j.cub.2003.08.032
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发表时间:
2003-09-30
期刊:
影响因子:
9.2
通讯作者:
Welte, MA
Welte, MA
中科院分区:
生物学1区
文献类型:
--
作者:
Gross, SP;Guo, Y;Welte, MA

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背景:马达驱动沿着微管转运是细胞器移动和定位的主要机制。许多货物通过使用负端和正端导向马达双向移动。这些货物如何进行控制的净transport.Results:使用遗传学,分子生物学和生物物理学相结合,我们已经确定了光环,一种新的调节剂的早期果蝇胚胎的脂滴运输。在缺乏Halo的胚胎中,脂滴的净运输(而不是其他货物的净运输)发生了特异性改变;在发育阶段,净运输是负端方向的,而正常情况下是正端方向的。这种逆转是由于在单个细胞器水平上改变了运动平衡;没有Halo,正端运动的行程距离和失速力减少,负端运动的行程距离和失速力增加。在发育过程中,halo mRNA在净正端转运启动时高度上调(第11期),在负端定向转运前不久其水平急剧下降(第111期)。外源性Halo可防止野生型胚胎在第III阶段转换为净负端运输,并在第11阶段诱导Halo突变体胚胎的净正端运输。这种调节机制可能是普遍的重要性,因为果蝇基因组编码一个家庭的相关蛋白质具有相似的序列,每个瞬时表达在不同domain.Conclusions:我们的结论是,晕作为一个方向性决定胚胎液滴运输,是第一个成员的一类新的运输监管机构。
Background: Motor-driven transport along microtubules is a primary cellular mechanism for moving and positioning organelles. Many cargoes move bidirectionally by using both minus and plus end-directed motors. How such cargoes undergo controlled net transport is unresolved.Results: Using a combination of genetics, molecular biology, and biophysics, we have identified Halo, a novel regulator of lipid droplet transport in early Drosophila embryos. In embryos lacking Halo, net transport of lipid droplets, but not that of other cargoes, is specifically altered; net transport is minus-end directed at developmental stages when it is normally plus-end directed. This reversal is due to an altered balance of motion at the level of individual organelles; without Halo, travel distances and stall forces are reduced for plus-end and increased for minus-end motion. During development, halo mRNA is highly upregulated just as net plus-end transport is initiated (phase 11), and its levels drop precipitously shortly before transport becomes minus-end directed (phase 111). Exogenously provided Halo prevents the switch to net minus-end transport in phase III in wild-type embryos and induces net plus-end transport during phase 11 in halo mutant embryos. This mechanism of regulation is likely to be of general importance because the Drosophila genome encodes a family of related proteins with similar sequences, each transiently expressed in distinct domains.Conclusions: We conclude that Halo acts as a directionality determinant for embryonic droplet transport and is the first member of a new class of transport regulators.