Liprin-α is required for photoreceptor target selection in Drosophila
Liprin-α is required for photoreceptor target selection in Drosophila
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DOI：
10.1073/pnas.0601185103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
Clandinin, Thomas R.
中科院分区：
文献类型：
--
作者：
Choe, Kwang-Min;Prakash, Saurabh;Clandinin, Thomas R.
经典钙粘蛋白介导的轴突和树突之间的相互作用对目标选择和突触组装至关重要。然而，控制这些相互作用的分子机制尚不完全清楚。在果蝇的视觉系统中，光感受器（R细胞）轴突及其靶标都需要n -钙粘蛋白来介导R细胞靶标选择所需的稳定相互作用。在这里，我们确定支架蛋白lipin -alpha在这个过程中是一个关键的组成部分。我们在影响R1-R6光感受器突触连接模式的基因筛选中分离出lipin - α突变。利用眼特异性嵌合体，我们证明了先前未描述的liprinα在靶标选择中的轴突功能：在R1-R6细胞的所有亚型中，liprinα都需要是细胞自主的，以便其轴突到达靶标。由于lipin -alpha、受体酪氨酸磷酸酶LAR和n-钙粘蛋白在R1-R6细胞中具有质量相似的突变表型，并且在R细胞及其突触靶标中共表达，我们推断这三个基因在靶向过程中作用于同一步骤。然而，与n-钙粘蛋白不同的是，无论是lipin - α还是LAR都不需要突触后R细胞投射到正确的目标。因此，与n -钙粘蛋白不同，这两种蛋白在轴突和树突之间是功能不对称的。我们提出突触形成前连接突触前细胞和突触后细胞的粘附机制可能在这两个区室中受到不同的调节。
Classical cadherin-mediated interactions between axons and dendrites are critical to target selection and synapse assembly. However, the molecular mechanisms by which these interactions are controlled are incompletely understood. In the Drosophila visual system, N-cadherin is required in both photoreceptor (R cell) axons and their targets to mediate stabilizing interactions required for R cell target selection. Here we identify the scaffolding protein Liprin-alpha as a critical component in this process. We isolated mutations in Liprin-alpha in a genetic screen for mutations affecting the pattern of synaptic connections made by R1-R6 photoreceptors. Using eye-specific mosaics, we demonstrate a previously undescribed, axonal function for Liprin-alpha in target selection: Liprin-alpha is required to be cell-autonomous in all subtypes of R1-R6 cells for their axons to reach their targets. Because Liprin-alpha, the receptor tyrosine phosphatase LAR, and N-cadherin share qualitatively similar mutant phenotypes in R1-R6 cells and are coexpressed in R cells and their synaptic targets, we infer that these three genes act at the same step in the targeting process. However, unlike N-cadherin, neither Liprin-alpha nor LAR is required postsynaptically for R cells to project to their correct targets. Thus, these two proteins, unlike N-cadherin, are functionally asymmetric between axons and dendrites. We propose that the adhesive mechanisms that link pre- and postsynaptic cells before synapse formation may be differentially regulated in these two compartments.