The seven-pass transmembrane cadherin Flamingo controls dendritic self-avoidance via its binding to a LIM domain protein, Espinas, in Drosophila sensory neurons
The seven-pass transmembrane cadherin Flamingo controls dendritic self-avoidance via its binding to a LIM domain protein, Espinas, in Drosophila sensory neurons
复制标题
DOI：
10.1101/gad.16531611
复制
发表时间：
2011-09-15
影响因子：
10.5
通讯作者：
Uemura, Tadashi
中科院分区：
文献类型：
--
作者：
Matsubara, Daisuke;Horiuchi, Shin-ya;Uemura, Tadashi
火烈鸟钙粘蛋白家族的成员在许多不同的神经发育的体内环境中是必需的。即便如此，该家族下游的分子身份仍然知之甚少。在这里，我们表明，LIM结构域蛋白，Espinas（ESN），结合到细胞内的Flamingo（FMI）的质膜结构域，这Fmi-ESN相互作用eleventh果蝇感觉神经元的树突状分支之间的排斥。在野生型幼虫中，同一IV类树突状分支神经元的分支以彼此最小的重叠实现其二维感受野的有效覆盖。然而，这种自我回避在fmi亚型突变体、esn敲除纯合子和fmi/esn反式杂合子中被破坏。一个功能性的融合蛋白，Fmi：3eGFP，定位在大多数的分支尖端，并在异源系统中，装配的Esn在细胞接触位点需要其LIM结构域和Fmi。我们进一步表明，控制上皮平面细胞极性（PCP）的基因，如货车Gogh（旺）和RhoA，也是自我回避所必需的，fmi基因与这些位点相互作用。在这些和其他结果的基础上，我们提出，Fmi-Esn复合物，连同PCP调节剂和Tricorned（Trc）信号通路，执行异神经元树突分支之间的排斥相互作用。
Members of the Flamingo cadherin family are required in a number of different in vivo contexts of neural development. Even so, molecular identities downstream from the family have been poorly understood. Here we show that a LIM domain protein, Espinas (Esn), binds to an intracellular juxtamembrane domain of Flamingo (Fmi), and that this Fmi-Esn interplay elicits repulsion between dendritic branches of Drosophila sensory neurons. In wild-type larvae, branches of the same class IV dendritic arborization neuron achieve efficient coverage of its two-dimensional receptive field with minimum overlap with each other. However, this self-avoidance was disrupted in a fmi hypomorphic mutant, in an esn knockout homozygote, and in the fmi/esn trans-heterozygote. A functional fusion protein, Fmi:3eGFP, was localized at most of the branch tips, and in a heterologous system, assembly of Esn at cell contact sites required its LIM domain and Fmi. We further show that genes controlling epithelial planar cell polarity (PCP), such as Van Gogh (Vang) and RhoA, are also necessary for the self-avoidance, and that fmi genetically interacts with these loci. On the basis of these and other results, we propose that the Fmi-Esn complex, together with the PCP regulators and the Tricornered (Trc) signaling pathway, executes the repulsive interaction between isoneuronal dendritic branches.