title: 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.
authors.affiliation: Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 Quai Ernest Ansermet, Geneva 1211, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Derivery
authors.affiliation: Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 Quai Ernest Ansermet, Geneva 1211, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Seum
authors.affiliation: Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 Quai Ernest Ansermet, Geneva 1211, Switzerland.
authors.forename: Alicia
authors.initials: A
authors.lastname: Daeden
authors.affiliation: Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 Quai Ernest Ansermet, Geneva 1211, Switzerland.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Loubéry
authors.affiliation: Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 Quai Ernest Ansermet, Geneva 1211, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Holtzer
authors.affiliation: Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Strasse 38, 01187 Dresden, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jülicher
authors.affiliation: Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 Quai Ernest Ansermet, Geneva 1211, Switzerland.
authors.forename: Marcos
authors.initials: M
authors.lastname: Gonzalez-Gaitan
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division / Q000502:physiology*; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics; D011992:Endosomes / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D017384:Sequence Deletion; D061905:Single-Domain Antibodies; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D061905:Single-Domain Antibodies; C553301:patronin protein, Drosophila; C481339:KLP10A protein, Drosophila; D016547:Kinesins