Mark Fortini
National Cancer Institute at Frederick, National Institutes of Health (NIH), United States of AmericaThis paper presents a new cell biological mechanism, involving directional transmission of endosomes during cell division, in which a Drosophila sensory organ precursor (SOP) gives rise to its daughter cells pIIa and pIIb. As a result of this mechanism, Notch- and Delta-containing endosomes that have already formed in the SOP prior to its cell division are preferentially sorted into one daughter cell (pIIa), conferring an increase in Notch signaling to pIIa compared to pIIb.
During SOP mitosis, different mechanisms involving asymmetric segregation of the Notch inhibitory factor, Numb, as well as asymmetric endocytosis of the Notch ligand, Delta, lead to biases in Notch signaling between the pIIa and pIIb cells. In this new study, a distinct mechanism has been uncovered that also contributes to biased Notch signaling in the SOP lineage. In contrast to the earlier known mechanisms, which are initiated during the cell division that generates two different daughter cells pIIa and pIIb from the parental SOP cell, the new mechanism involves endosomes that are already present in the SOP prior to its division. The SOP contains specialized endosomes bearing Notch and Delta and also marked by the Sara protein. These Sara endosomes contain gamma-secretase-cleaved Notch and thus are actively contributing to Notch signaling. Remarkably, the Sara-positive endosomes move preferentially from the SOP cell into its pIIa daughter rather than its pIIb daughter, leading to increased Notch signaling in pIIa compared to pIIb. This mechanism reinforces the other asymmetrical signaling mechanisms that operate in the SOP lineage, ensuring that one daughter cell reliably achieves a higher level of Notch signaling relative to its sibling cell produced in the same mitotic event. The direct transmission of Sara endosomes is a striking example of how the asymmetric movement of a specific intracellular organelle from one cell into another can be exploited to modulate an important developmental signaling pathway.
Nature. 2009 Mar 18.
Directional Delta and Notch trafficking in Sara endosomes during asymmetric cell division.
Coumailleau F, Fürthauer M, Knoblich JA, González-Gaitán M.
[1] Departments of Biochemistry and Molecular Biology, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland [2] These authors contributed equally to this work.
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. 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. 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.
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