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Endocytosis by Numb breaks Notch symmetry at cytokinesis

Nat Cell Biol. 2012 Jan 22;14(2):131-9. doi: 10.1038/ncb2419.

Abstract

Cell-fate diversity can be generated by the unequal segregation of the Notch regulator Numb at mitosis in both vertebrates and invertebrates. Whereas the mechanisms underlying unequal inheritance of Numb are understood, how Numb antagonizes Notch has remained unsolved. Live imaging of Notch in sensory organ precursor cells revealed that nuclear Notch is detected at cytokinesis in the daughter cell that does not inherit Numb. Numb and Sanpodo act together to regulate Notch trafficking and establish directional Notch signalling at cytokinesis. We propose that unequal segregation of Numb results in increased endocytosis in one daughter cell, hence asymmetry of Notch at the cytokinetic furrow, directional signalling and binary fate choice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Nucleus / metabolism
  • Cytokinesis*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Dynamins / genetics
  • Dynamins / metabolism
  • Endocytosis*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Juvenile Hormones / genetics
  • Juvenile Hormones / metabolism*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microscopy, Fluorescence
  • Mutation
  • Protein Binding
  • RNA Interference
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Time-Lapse Imaging

Substances

  • Drosophila Proteins
  • Juvenile Hormones
  • Luminescent Proteins
  • Microfilament Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • numb protein, Drosophila
  • spdo protein, Drosophila
  • Green Fluorescent Proteins
  • Dynamins
  • shi protein, Drosophila