During mitosis, some cellular contents can be distributed randomly, whereas others must be distributed evenly between daughter cells. For example, components of the transforming growth factor-β (TGFβ) pathway must be distributed evenly for viable development; the TGFβ pathway makes sense of the decapentaplegic (Dpp) morphogen gradient in Drosophila melanogaster wings to generate positional gene expression. In Science, Bökel et al. show that the endosomal protein Sara recruits thickveins (Tkv), the Dpp receptor, to a subset of endosomes that are distributed evenly in mitosis.

Researchers first showed that Sara is localized with Dpp and Tkv in ∼10% of early endosomal signalling compartments. Using immunostaining, Sara-positive endosomes were shown to cluster at the spindle midzone during anaphase. During cytokinesis, however, these endosomes were separated into two equal subpopulations at opposite ends of the central spindle, and they were thereby distributed evenly between the daughter cells upon division. By contrast, other endosomal compartments, such as lysosomes, were distributed randomly. Mutations of sara showed that Sara recruits Tkv to the evenly distributed endosomes, but that it does not function in the even distribution of these endosomes.

...Sara targets Tkv to the endosomes that are evenly distributed during mitosis to ensure the maintenance of the pMad gradient through mitosis.

To examine the biological effects of Sara, Bökel and colleagues quantified the levels of phosphorylated Mad (pMad), a transcription factor that is phosphorylated along a gradient that parallels the Dpp gradient. Under wild-type conditions, pMad levels were equal between daughter cells (as would be necessary to maintain a stable pMad gradient across the fly wing). By contrast, pMad levels showed a variability of up to 2.5-fold between sara-mutant daughter cells. So, Sara targets Tkv to the endosomes that are evenly distributed during mitosis to ensure the maintenance of the pMad gradient through mitosis.

Interestingly, wings of the few sara-mutant survivors did not have large-scale Dpp-related patterning phenotypes, indicating that an alternative mechanism can correct abnormal Dpp signalling. Elevated levels of apoptosis were observed in sara-mutant wings, and sara-mutant apoptotic cells showed elevated pMad levels. By contrast, cells with inappropriately low pMad levels did not undergo apoptosis. Therefore, cells seem to have a semi-efficient mechanism that can sense inappropriately high signalling levels and then induce apoptosis.

So, just as a mother might reward or punish her children to make them share, a mother cell uses a double mechanism to ensure the equal sharing of its signalling components between daughter cells: endosomes that contain crucial signalling molecules (including Tkv, as recruited by Sara) are equally distributed during mitosis, and signalling-component abnormalities can be sensed and handled by apoptosis.