Das Gishnu, Jenny Andreas, Klein Thomas J, Eaton Suzanne, Mlodzik Marek
Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Development. 2004 Sep;131(18):4467-76. doi: 10.1242/dev.01317. Epub 2004 Aug 11.
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.
果蝇眼中的平面细胞极性(PCP)是由光感受器R3和R4不同的命运特化建立的,并受卷曲蛋白(Fz)/PCP信号通路调控。在PCP蛋白响应Fz/PCP信号不对称定位于细胞相反两极之前,它们在顶端均匀共定位。关于顶端定位如何维持知之甚少。我们提供证据表明,PCP蛋白迪戈(Dgo)促进非典型钙黏蛋白家族成员弗拉明戈(Fmi)顶端定位的维持,而Fmi本身是其他PCP因子顶端定位所必需的。Dgo的这一功能与普里克(Pk)和斜视(Stbm)冗余,且仅在双突变组织中明显。我们表明,Dgo最初与膜的结合依赖于Fz,并且Dgo通过其锚蛋白重复序列与Stbm和Pk发生物理相互作用,为PCP多蛋白复合体提供了证据。这些相互作用提示了一个由Fz启动的正反馈环,该正反馈环通过Fmi导致其他PCP因子的顶端维持。