Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes

Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes
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DOI:
10.1242/dev.01317
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发表时间:
2004-09-01
期刊:
影响因子:
4.6
通讯作者:
Mlodzik, M
Mlodzik, M
中科院分区:
生物学2区
文献类型:
--
作者:
Das, G;Jenny, A;Mlodzik, M

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果蝇眼的平面细胞极性(PCP)是由光感受器R3和R4的不同命运决定的,并受FrizzledFZ/PCP信号通路的调节。在PCP蛋白响应FZ/PCP信号而变得不对称地定位到细胞的相反两极之前,它们被统一地顶端共定位。关于根尖定位是如何维持的,人们知之甚少。我们提供的证据表明,PCP蛋白Diego(DGO)促进了非典型钙粘连蛋白家族成员Flamingo(Fmi)的心尖定位的维持,而Fmi本身是其他PCP因子的心尖定位所必需的。DGO的这一功能在PK和STBM中是多余的,并且仅在双突变组织中可察觉。我们证明了DGO最初的膜结合依赖于FZ,并且DGO通过其Ankyrin重复序列与Stbm和PK物理相互作用,为PCP多蛋白复合体提供了证据。这些相互作用表明,FZ启动了一个正反馈循环,导致通过FMI维持其他PCP因子的顶端。
Planar cell polarity (PCP) in the Drosophila eye is established by the distinct fate specifications of photoreceptors R3 and R4, and is regulated by the Frizzled (Fz)/PCP signaling pathway. Before the PCP proteins become asymmetrically localized to opposite poles of the cell in response to Fz/PCP signaling, they are uniformly apically colocalized. Little is known about how the apical localization is maintained. We provide evidence that the PCP protein Diego (Dgo) promotes the maintenance of apical localization of Flamingo (Fmi), an atypical Cadherin-family member, which itself is required for the apical localization of the other PCP factors. This function of Dgo is redundant with Prickle (Pk) and Strabismus (Stbm), and only appreciable in double mutant tissue. We show that the initial membrane association of Dgo depends on Fz, and that Dgo physically interacts with Stbm and Pk through its Ankyrin repeats, providing evidence for a PCP multiprotein complex. These interactions suggest a positive feedback loop initiated by Fz that results in the apical maintenance of other PCP factors through Fmi.