Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division

Nat Commun. 2018 Feb 21;9(1):737. doi: 10.1038/s41467-018-03077-3.

Abstract

Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity in general. In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its differentiation. Here we discover that Numb PTB domain, using two distinct binding surfaces, recognizes repeating motifs within Pon in a previously unrecognized mode. The multivalent Numb-Pon interaction leads to high binding specificity and liquid-liquid phase separation of the complex. Perturbations of the Numb/Pon complex phase transition impair the basal localization of Numb and its subsequent suppression of Notch signaling during NB asymmetric divisions. Such phase-transition-mediated protein condensations on distinct membrane cortices may be a general mechanism for various cell polarity regulatory complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Asymmetric Cell Division*
  • Carrier Proteins / physiology*
  • Cell Differentiation
  • Cell Membrane / metabolism
  • Cell Polarity
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology*
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Juvenile Hormones / physiology*
  • Neurogenesis*
  • Neurons / metabolism*
  • Protein Binding
  • Protein Domains
  • Signal Transduction

Substances

  • Carrier Proteins
  • Drosophila Proteins
  • Juvenile Hormones
  • PON protein, Drosophila
  • numb protein, Drosophila