Endosomes for Asymmetry

Science Signaling  28 Apr 2009:
Vol. 2, Issue 68, pp. ec147
DOI: 10.1126/scisignal.268ec147

Sensory organ precursor (SOP) cells undergo asymmetric cell division to produce a pIIa cell, which sends a Delta signal, and a pIIb cell, which receives the Delta signal and responds with Notch signaling. Coumailleau et al. provide evidence that asymmetric distribution of endosomes that are positive for the protein Sara, which is involved in trafficking internalized Delta and Notch, contributes to the asymmetry of the daughter cells produced by division of the SOP. Live-cell imaging of endosomes labeled with fluorophore-conjugated antibodies to Delta or Notch showed that after 10 minutes Delta and Notch colocalized with Sara and accumulated in endosomes that were targeted to the central spindle such that upon mitosis the endosomes segregated into the pIIa daughter cell. Sara is also present in the cytoplasm, and this pool of Sara was evenly distributed into the pIIa and pIIb daughter cells after mitosis. Sara was not required for the asymmetric distribution of Notch and Delta into the daughter cells, and Notch and Delta were not required for asymmetric distribution of Sara-positive endosomes. However, overexpression of Sara results in aberrant distribution of both early endosomes (normally evenly divided between the two daughter cells) into the pIIa cells and Sara-positive endosomes in the pIIb cells, suggesting that the system becomes saturated. By expressing a Rab5 mutant that results in the production of a single large Sara-positive endosome, the authors showed that when this endosome properly segregated, the cells divided to produce the pIIa and pIIb daughters, whereas when this endosome was mistargeted, the SOP produced two pIIa cells. The authors suggested that targeting of this Notch signaling endosome may deplete signaling molecules from the cell in which it is absent and may supply these molecules to the cell receiving it. In support of this, before division the Sara-positive endosome in the SOP contains Delta and both the extracellular and intracellular domains of Notch (Notch is cleaved to produce the intracellular domain that is a transcriptional regulator). After mitosis, the endosomes are no longer positive for the intracellular domain of Notch, suggesting that it may have been released to act in the nucleus.

F. Coumailleau, M. Fürthauer, J. A. Knoblich, M. González-Gaitán, Directional Delta and Notch trafficking in Sara endosomes during asymmetric cell division. Nature 458, 1051–1055 (2009). [PubMed]