Numb has a paradoxical role in cell fate: when a neuronal progenitor divides, Numb keeps one daughter in the progenitor state by inhibiting Notch. Yet Numb is also needed for neuronal differentiation. To solve this mystery, Zhong's group fished for Numb's binding partners. They found a Golgi protein called ACBD3 whose brief cytosolic appearances during mitosis turned Numb into a supporter of the progenitor fate.
During progenitor division, Numb is sent to one daughter, where it carries on the progenitor fate. The authors found that Numb's binding to ACBD3 was required for this progenitor maintenance. This binding was only possible during mitosis, when the Golgi disassembled and ACBD3 was released into the cytosol to meet Numb. Given this narrow window of opportunity, Zhong figures, “fate must be determined before cells are even finished dividing. After that, it might be just maintenance.”
The lack of Numb in the other daughter allowed for Notch-orchestrated neuronal differentiation. But later, this neuron's survival depended on newly made Numb and its ACBD3-free activity. Forcing ACBD3 to remain in the cytosol inhibited neurogenesis.
Other stem cells probably also depend on Numb and the Golgi-organized timing of ACBD3 release. And there's no reason to assume that ACBD3 is the only protein that exploits Golgi dynamics. “Golgi fragmentation in lots of vertebrate cells may be doing more than divvying up the organelle,” says Zhong.