Directional Delta and Notch trafficking in Sara endosomes during asymmetric cell division
Directional Delta and Notch trafficking in Sara endosomes during asymmetric cell division
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DOI：
10.1038/nature07854
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发表时间：
2009-04-23
期刊：
影响因子：
64.8
通讯作者：
Gonzalez-Gaitan, M.
中科院分区：
文献类型：
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作者：
Coumailleau, F.;Fuerthauer, M.;Gonzalez-Gaitan, M.
在果蝇感觉器官前体（SOP）不对称分裂后，内吞作用在Notch信号传导过程中起着至关重要的作用：定向信号传导是由配体Delta和Notch效应物Sanpodo在SOP子细胞pIIb中的差异内吞作用介导的（1-3）。在这里，我们展示了一种新的定向信号传导机制，该机制基于已经内化在SOP中的Delta和Notch分子的运输，并随后靶向另一个子细胞pIIa。内化了Delta和Notch到由Sara蛋白标记的核内体（4,5）。在SOP有丝分裂过程中，含有Notch和Delta的Sara核内体移动到中央纺锤体，然后移动到pIIa。随后，在pIIa（而不是pIIb）中，Notch在Sara核内体中以γ -分泌酶和Delta内化依赖的方式出现断裂，表明细胞内Notch尾的释放激活了Notch靶基因。因此，我们发现了一种新的偏倚信号传导机制，甚至在子细胞中发生Sanpodo和Delta的不对称内吞作用之前：在SOP有丝分裂期间，Delta和含有Notch的Sara内体的不对称靶向会增加pIIa中的Notch信号传导，减少pIIb中的Notch信号传导。
Endocytosis has a crucial role during Notch signalling after the asymmetric division of fly sensory organ precursors (SOPs): directional signalling is mediated by differential endocytosis of the ligand Delta and the Notch effector Sanpodo in one of the SOP daughters, pIIb(1-3). Here we show a new mechanism of directional signalling on the basis of the trafficking of Delta and Notch molecules already internalized in the SOP and subsequently targeted to the other daughter cell, pIIa. Internalized Delta and Notch traffic to an endosome marked by the protein Sara(4,5). During SOP mitosis, Sara endosomes containing Notch and Delta move to the central spindle and then to pIIa. Subsequently, in pIIa (but not in pIIb) Notch appears cleaved in Sara endosomes in a gamma-secretase-and Delta internalization-dependent manner, indicating that the release of the intracellular Notch tail to activate Notch target genes has occurred. We thus uncover a new mechanism to bias signalling even before asymmetric endocytosis of Sanpodo and Delta takes place in the daughter cells: already during SOP mitosis, asymmetric targeting of Delta and Notch-containing Sara endosomes will increase Notch signalling in pIIa and decrease it in pIIb.