Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube growth.

Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube growth.
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Whacked 和 Rab35 极化动力蛋白运动复合体依赖性无缝管生长。

DOI:
10.1038/ncb2454
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发表时间:
2012
影响因子:
21.3
通讯作者:
Ghabrial,AminS
Ghabrial,AminS
中科院分区:
生物学1区
文献类型:
--
作者:
Schottenfeld-Roames,Jodi;Ghabrial,AminS

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无缝管在细胞内形成,没有细胞与细胞或自细胞连接。此类管已在各个门中被描述,但尽管其结构简单,但仍然神秘。在果蝇中,气管终末细胞内发现了无缝管,这些细胞有数十个延伸数百微米的分支突起。我们发现动力蛋白运动复合体的多个成分的突变阻碍了无缝管的生长,从而提高了通过沿微管负端定向运输顶膜成分形成管腔膜的可能性。无缝管的生长通过 Rab35 及其顶膜定位的 GAP(Whacked)沿近远轴极化。引人注目的是,whacked(或 Rab35 的组成型激活)的缺失会导致终末细胞分支尖端的管过度生长,而 Whacked(或显性失活 Rab35)的过度表达会导致终末细胞核周围异位管的形成。因此,囊泡运输在无缝管的制造和成型中起着关键作用。
Seamless tubes form intracellularly without cell–cell or autocellular junctions. Such tubes have been described across phyla, but remain mysterious despite their simple architecture. InDrosophila, seamless tubes are found within tracheal terminal cells, which have dozens of branched protrusions extending hundreds of micrometres. We find that mutations in multiple components of the dynein motor complex block seamless tube growth, raising the possibility that the lumenal membrane forms through minus-end-directed transport of apical membrane components along microtubules. Growth of seamless tubes is polarized along the proximodistal axis by Rab35 and its apical membrane-localized GAP, Whacked. Strikingly, loss ofwhacked(or constitutive activation of Rab35) leads to tube overgrowth at terminal cell branch tips, whereas overexpression of Whacked (or dominant-negative Rab35) causes formation of ectopic tubes surrounding the terminal cell nucleus. Thus, vesicle trafficking has key roles in making and shaping seamless tubes.
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