Reggie-1/flotillin-2 promotes secretion of the long-range signalling forms of Wingless and Hedgehog in Drosophila.
Reggie-1/flotillin-2 promotes secretion of the long-range signalling forms of Wingless and Hedgehog in Drosophila.
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DOI：
10.1038/sj.emboj.7601981
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发表时间：
2008-02-06
期刊：
影响因子：
11.4
通讯作者：
Basler, Konrad
中科院分区：
文献类型：
--
作者：
Katanaev, Vladimir L.;Solis, Gonzalo P.;Hausmann, George;Buestorf, Silke;Katanayeva, Natalya;Schrock, Yvonne;Stuermer, Claudia A. O.;Basler, Konrad
脂质修饰的形态因子Wnt和Hedgehog在孤立状态下扩散较差，但可以在体内长距离传播，这预示着这些形态因子存在两种不同的形式。第一种是流动性差，激活短程靶基因。第二个是专门为有效扩散而包装的，以诱导远程目标。参与这两种形式的鉴别分泌的亚细胞机制仍然难以捉摸。Wnt和Hedgehog基因可以与膜微域结合，但这种结合的功能尚不清楚。本研究表明，细胞膜微域的主要蛋白组分reggie-1/ flotilin -2在果蝇Wnt和Hedgehog基因的分泌和传播中发挥重要作用。Reggie-1功能缺失导致形态因子的扩散减少，而其过表达刺激Wnt和Hedgehog的分泌并扩大其扩散。由此产生的形态梯度变化对近程和远程目标的影响不同。reggie-1的作用似乎是针对Wnt和Hedgehog特异的。这些数据表明reggie-1是Wnt和Hedgehog分泌通路的重要组成部分，致力于形成这些形态因子的移动池。
The lipid-modified morphogens Wnt and Hedgehog diffuse poorly in isolation yet can spread over long distances in vivo, predicting existence of two distinct forms of these mophogens. The first is poorly mobile and activates short-range target genes. The second is specifically packed for efficient spreading to induce long-range targets. Subcellular mechanisms involved in the discriminative secretion of these two forms remain elusive. Wnt and Hedgehog can associate with membrane microdomains, but the function of this association was unknown. Here we show that a major protein component of membrane microdomains, reggie-1/flotillin-2, plays important roles in secretion and spreading of Wnt and Hedgehog in Drosophila. Reggie-1 loss-of-function results in reduced spreading of the morphogens, while its overexpression stimulates secretion of Wnt and Hedgehog and expands their diffusion. The resulting changes in the morphogen gradients differently affect the short- and long-range targets. In its action reggie-1 appears specific for Wnt and Hedgehog. These data suggest that reggie-1 is an important component of the Wnt and Hedgehog secretion pathway dedicated to formation of the mobile pool of these morphogens.
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