The Drosophila GIPC homologue can modulate myosin based processes and planar cell polarity but is not essential for development.
The Drosophila GIPC homologue can modulate myosin based processes and planar cell polarity but is not essential for development.
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DOI：
10.1371/journal.pone.0011228
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发表时间：
2010-06-21
期刊：
影响因子：
3.7
通讯作者：
Mlodzik M
中科院分区：
文献类型：
--
作者：
Djiane A;Mlodzik M
除了普遍存在的顶-底（A/B）轴之外，上皮通常显示上皮平面内垂直于A/B轴的极化。这种平面细胞极性（PCP）例如在哺乳动物内耳的耳蜗中或在（几乎）所有果蝇属成年外部结构中的静纤毛的规则排列中是明显的。GIPC（GAIP相互作用蛋白，C末端）首先在哺乳动物中被鉴定，并与Gαi GT3激活蛋白RGS-GAIP结合。他们已被提议采取行动的G蛋白偶联复合物控制囊泡运输。尽管已发现GIPC与包括Frizzled受体在内的多种蛋白质结合，这些蛋白质参与PCP的形成，但几乎没有关于GIPC功能作用的体内证据。我们在这里表明，过表达的果蝇dGIPC改变PCP产生的翅膀。然而，我们无法发现dGIPC与果蝇受体Fz 1和Fz 2之间的任何结合。过表达的dGIPC的作用可能是由于通过肌球蛋白对肌动蛋白细胞骨架的作用，因为它几乎完全被去除肌球蛋白VI/jaguar基因的基因组拷贝所抑制。令人惊讶的是，虽然dGIPC可以干扰PCP的产生和基于肌球蛋白的过程，但dGIPC的功能完全丧失使存活的成年人没有PCP或其他可检测到的缺陷，这证明了dGIPC在生存力和正常果蝇发育中的非必需作用。
Epithelia often show, in addition to the ubiquitous apico-basal (A/B) axis, a polarization within the plane of the epithelium, perpendicular to the A/B axis. Such planar cell polarity (PCP) is for example evident in the regular arrangement of the stereocilia in the cochlea of the mammalian inner ear or in (almost) all Drosophila adult external structures. GIPCs (GAIP interacting protein, C terminus) were first identified in mammals and bind to the Gαi GTPase activating protein RGS-GAIP. They have been proposed to act in a G-protein coupled complex controlling vesicular trafficking. Although GIPCs have been found to bind to numerous proteins including Frizzled receptors, which participate in PCP establishment, there is little in vivo evidence for the functional role(s) of GIPCs. We show here that overexpressed Drosophila dGIPC alters PCP generation in the wing. We were however unable to find any binding between dGIPC and the Drosophila receptors Fz1 and Fz2. The effect of overexpressed dGIPC is likely due to an effect on the actin cytoskeleton via myosins, since it is almost entirely suppressed by removing a genomic copy of the Myosin VI/jaguar gene. Surprisingly, although dGIPC can interfere with PCP generation and myosin based processes, the complete loss-of-function of dGIPC gives viable adults with no PCP or other detectable defects arguing for a non-essential role of dGIPC in viability and normal Drosophila development.
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