Polarized endosome dynamics by spindle asymmetry during asymmetric cell division

Abstract

During asymmetric division, fate determinants at the cell cortex segregate unequally into the two daughter cells. It has recently been shown that Sara (Smad anchor for receptor activation) signalling endosomes in the cytoplasm also segregate asymmetrically during asymmetric division. Biased dispatch of Sara endosomes mediates asymmetric Notch/Delta signalling during the asymmetric division of sensory organ precursors in Drosophila. In flies, this has been generalized to stem cells in the gut and the central nervous system, and, in zebrafish, to neural precursors of the spinal cord. However, the mechanism of asymmetric endosome segregation is not understood. Here we show that the plus-end kinesin motor Klp98A targets Sara endosomes to the central spindle, where they move bidirectionally on an antiparallel array of microtubules. The microtubule depolymerizing kinesin Klp10A and its antagonist Patronin generate central spindle asymmetry. This asymmetric spindle, in turn, polarizes endosome motility, ultimately causing asymmetric endosome dispatch into one daughter cell. We demonstrate this mechanism by inverting the polarity of the central spindle by polar targeting of Patronin using nanobodies (single-domain antibodies). This spindle inversion targets the endosomes to the wrong cell. Our data uncover the molecular and physical mechanism by which organelles localized away from the cellular cortex can be dispatched asymmetrically during asymmetric division.

Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging

“…Here we could confirm this observation and report for the first time that it is equally true for endocytosed molecular agents like Alexa Fluor dextran. This is perhaps not so surprising in light of the recent finding that asymmetric inheritance of vesicles is a naturally occurring cellular process 37 .…”

“…In addition, it has been reported that nanomaterials trapped in endolysosomal vesicles are not distributed equally over daughter cells upon cell division 30,34,35 . While this process has been proposed to be a protective mechanism where the daughter cell with the highest NP load can be sacrificed in favour of the daughter cell with the lowest NP content 29,36 , recent findings show that asymmetric inheritance of vesicles is an inherent cell-biological phenomenon 37 . For quantitative cell tracking applications asymmetric inheritance of contrast agents over daughter cells is disadvantageous as it hinders accurate quantification of cell numbers over time, apart from the fact that the brightest signals are coming from cells that are suffering from the highest cytotoxicity.…”

The Notch meeting: an odyssey from structure to function

“…pIIa because of the asymmetric polymerization/de-polymerization of microtubules (Derivery et al, 2015).…”

The ins(ide) and outs(ide) of asymmetric stem cell division

“…Asymmetric segregation of Sara endosomes plays an important role in the asymmetric divisions of sensory organ precursors and intestinal stem cells in Drosophila as well as the neural precursors in the zebrafish spinal cord [18–20]. This process requires spindle asymmetry, which is generated by microtubule motors, to distribute Sara endosomes asymmetrically [21]. …”