Directional Delta and Notch trafficking in Sara endosomes during asymmetric cell division

被引:146
作者
Coumailleau, F. [1 ,2 ]
Fuerthauer, M. [1 ,2 ]
Knoblich, J. A. [3 ]
Gonzalez-Gaitan, M. [1 ,2 ]
机构
[1] Univ Geneva, Dept Biochem, CH-1211 Geneva 4, Switzerland
[2] Univ Geneva, Dept Mol Biol, CH-1211 Geneva 4, Switzerland
[3] Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria
基金
瑞士国家科学基金会;
关键词
RECEPTOR ACTIVATION; DROSOPHILA EMBRYOS; DOMAIN PROTEIN; FYVE DOMAIN; LOCALIZATION; ENDOCYTOSIS; SUPPRESSOR; PRESENILIN; SANPODO; FATE;
D O I
10.1038/nature07854
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1051 / 1055
页数:5
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