Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Neuron. 2011 Aug 11;71(3):447-59. doi: 10.1016/j.neuron.2011.06.040.
Neurons establish specific synaptic connections with their targets, a process that is highly regulated. Numerous cell adhesion molecules have been implicated in target recognition, but how these proteins are precisely trafficked and targeted is poorly understood. To identify components that affect synaptic specificity, we carried out a forward genetic screen in the Drosophila eye. We identified a gene, named ric1 homologue (rich), whose loss leads to synaptic specificity defects. Loss of rich leads to reduction of N-Cadherin in the photoreceptor cell synapses but not of other proteins implicated in target recognition, including Sec15, DLAR, Jelly belly, and PTP69D. The Rich protein binds to Rab6, and Rab6 mutants display very similar phenotypes as the rich mutants. The active form of Rab6 strongly suppresses the rich synaptic specificity defect, indicating that Rab6 is regulated by Rich. We propose that Rich activates Rab6 to regulate N-Cadherin trafficking and affects synaptic specificity.
神经元与其靶标建立特定的突触连接，这个过程受到高度调控。许多细胞黏附分子参与了靶标识别，但这些蛋白质如何被精确运输和靶向仍然知之甚少。为了鉴定影响突触特异性的成分，我们在果蝇眼中进行了正向遗传学筛选。我们鉴定了一个名为 ric1 同源物（rich）的基因，其缺失导致突触特异性缺陷。rich 的缺失导致光感受器细胞突触中的 N-钙黏蛋白减少，但不影响其他参与靶标识别的蛋白质，包括 Sec15、DLAR、Jelly belly 和 PTP69D。Rich 蛋白与 Rab6 结合，而 Rab6 突变体显示出与 rich 突变体非常相似的表型。Rab6 的活性形式强烈抑制了 rich 的突触特异性缺陷，表明 Rab6 受到 Rich 的调控。我们提出，Rich 激活 Rab6 来调节 N-钙黏蛋白的运输，并影响突触特异性。
