Knoblich studies fly sensory organ precursor (SOP) cells, which divide to form two cells—pIIa and pIIb—with different fates. Those fates are decided largely by Notch and its binding partner Delta. In pIIb, the asymmetry determinants Numb and Neuralized turn off Notch and increase the endocytosis that somehow activates Delta activity.
The Austrian team found that only in pIIb did Delta travel to a compartment resembling a recycling endosome. From here it could be sent back to the plasma membrane to activate Notch on pIIa. Some Delta endocytosis also happens in pIIa but, with no recycling endosome available, this Delta is sent to its destruction in a lysosome.
The recycling endosome protein Rab11 was present in both of the daughter cells, but only pIIb had centrosome-localized recycling endosomes labeled with Rab11 and the Rab11-binding protein Nuf. Overriding both the Numb and Rab11 pathways, but not either one by itself, resulted in a complete loss of asymmetry.
The work has uncovered not only a new pathway for asymmetric cell division but a more dramatic mode of regulation by the endocytic system. Endocytosis of select cargos has been known for some time to regulate signal transduction. “What is new,” says Knoblich, “is that for the first time a cell can regulate the endocytic pathway itself—the cell shuts off the recycling endosome. That is unprecedented.”