AP-1 Controls the Trafficking of Notch and Sanpodo toward E-Cadherin Junctions in Sensory Organ Precursors
AP-1 Controls the Trafficking of Notch and Sanpodo toward E-Cadherin Junctions in Sensory Organ Precursors
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DOI：
10.1016/j.cub.2010.12.010
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发表时间：
2011-01-11
期刊：
影响因子：
9.2
通讯作者：
Le Borgne, Roland
中科院分区：
文献类型：
--
作者：
Benhra, Najate;Lallet, Sylvie;Le Borgne, Roland
在黑腹果蝇中，外部感觉器官是从单一的感觉器官前体（SOP）发育而来的。SOP不对称分裂以产生子细胞，其命运由差异Notch激活控制。在这里，我们表明，网格蛋白适配器AP-1复合物，定位在反式高尔基体网络和再循环内体，作为一个负调节Notch信号。AP-1的失活导致Notch的配体依赖性激活，导致感觉器官内的命运转变。AP-1的缺失既不影响细胞极性，也不影响细胞命运决定因子Numb和Neuralized的不平等分离。相反，它导致Notch激活剂Sanpodo的顶端积累以及Sanpodo和Notch在SOP子细胞之间的界面处的稳定化，其中DE-钙粘蛋白被定位。内吞再循环试验表明，AP-1的行为，在再循环内体，以防止内化的Spdo从再循环到adherens连接。因为AP-1不能阻止Notch配体Delta的内吞和再循环，我们的数据表明DE-钙粘蛋白连接结构域可以作为发射台，通过该发射台内吞的Notch配体被运输用于信号传导。
In Drosophila melanogaster, external sensory organs develop from a single sensory organ precursor (SOP). The SOP divides asymmetrically to generate daughter cells, whose fates are governed by differential Notch activation. Here we show that the clathrin adaptor AP-1 complex, localized at the trans Golgi network and in recycling endosomes, acts as a negative regulator of Notch signaling. Inactivation of AP-1 causes ligand-dependent activation of Notch, leading to a fate transformation within sensory organs. Loss of AP-1 affects neither cell polarity nor the unequal segregation of the cell fate determinants Numb and Neuralized. Instead, it causes apical accumulation of the Notch activator Sanpodo and stabilization of both Sanpodo and Notch at the interface between SOP daughter cells, where DE-cadherin is localized. Endocytosis-recycling assays reveal that AP-1 acts in recycling endosomes to prevent internalized Spdo from recycling toward adherens junctions. Because AP-1 does not prevent endocytosis and recycling of the Notch ligand Delta, our data indicate that the DE-cadherin junctional domain may act as a launching pad through which endocytosed Notch ligand is trafficked for signaling.