Rho1 has multiple functions in Drosophila wing planar polarity.
Rho1 has multiple functions in Drosophila wing planar polarity.
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DOI：
10.1016/j.ydbio.2009.06.027
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发表时间：
2009-09-01
影响因子：
2.7
通讯作者：
Adler, Paul N.
中科院分区：
文献类型：
--
作者：
Yan, Jie;Lu, Qiuheng;Fang, Xiaolan;Adler, Paul N.
Fz信号转导通路控制脊椎动物和无脊椎动物平面细胞的极性。以前的数据表明，Rho1是果蝇fz通路的一个组成部分，但它是如何发挥作用的尚不清楚。在多个翼毛中存在G蛋白结合-福尔曼同源3(GBD-FH3)结构域，这表明Rho1可能通过与MWh结合并激活MWh而发挥作用。我们重新研究了Rho1在机翼平面极性中的作用，发现它具有多种功能。异常的Rho1活性导致毛发形成数量的变化、细胞形状和F-肌动蛋白的变化以及细胞连接的变化。利用Rho效应环突变的实验认为，这些表型是通过Rho1对细胞骨架的影响而不是通过对转录的影响来调节的。我们发现Rho1和MWh之间有很强的正遗传相互作用，Rho1调控MWh蛋白的积累，并且这两种蛋白可以免疫共沉淀。MWh GBD：FH3结构域足以与Rho1进行免疫共沉淀，与介导相互作用的这个结构域一致。然而，进一步的实验表明，Rho1在翅分化中的作用并不局限于与MWh的相互作用。我们通过基因实验证实，在没有MWh的情况下，Rho1可以影响毛发的形态发生，并且Rho1活性的中断可能会干扰上游fz途径蛋白的Z字形积累模式。因此，我们的结果认为，除了与MWH的相互作用外，Rho1还具有平行于fz并位于fz上游的机翼平面极性功能。上游功能可能是一种间接的功能，与PCP蛋白复合体积累所需的正常顶端基极性和黏附连接有关。
The frizzled (fz) signaling/signal transduction pathway controls planar cell polarity in both vertebrates and invertebrates. Previous data implicated Rho1 as a component of the fz pathway in Drosophila but it was unclear how it functioned. The existence of a G Protein Binding -Formin Homology 3 (GBD-FH3) domain in Multiple Wing Hairs, a downstream component of the pathway suggested that Rho1 might function by binding to and activating Mwh. We re-examined role of Rho1 in wing planar polarity and found it had multiple functions. Aberrant Rho1 activity led to changes in the number of hairs formed, changes in cell shape and F-actin and changes in cellular junctions. Experiments that utilized Rho effector loop mutations argued that these phenotypes were mediated by effects of Rho1 on the cytoskeleton and not by effects on transcription. We found strong positive genetic interactions between Rho1 and mwh, that Rho1 regulated the accumulation of Mwh protein and that these two proteins could be co-immunoprecipitated. The Mwh GBD:FH3 domain was sufficient for co-immunoprecipitation with Rho1, consistent with this domain mediating the interaction. However, further experiments showed that Rho1 function in wing differentiation was not limited to interacting with Mwh. We established by genetic experiments that Rho1 could influence hair morphogenesis in the absence of mwh and that the disruption of Rho1 activity could interfere with the zig zag accumulation pattern of upstream fz pathway proteins. Thus, our results argue that in addition to its interaction with Mwh Rho1 has functions in wing planar polarity that are parallel to and upstream of fz. The upstream function may be an indirect one and associated with the requirement for normal apical basal polarity and adherens junctions for the accumulation of PCP protein complexes.
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影响因子：
1.2
作者：
Gregory, Stephen L.;Shandala, Tetyana;Saint, Robert
通讯作者：
Saint, Robert
影响因子：
2.7
作者：
BUENZOW, DE;HOLMGREN, R
通讯作者：
HOLMGREN, R
影响因子：
3.3
作者：
He, Y;Fang, XL;Adler, PN
通讯作者：
Adler, PN
DOI：
10.1083/jcb.200709005
发表时间：
2008-01-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hickson GR;O'Farrell PH
通讯作者：
O'Farrell PH
影响因子：
11.8
作者：
Feiguin, F;Hannus, M;Eaton, S
通讯作者：
Eaton, S