Dynamic centriolar localization of Polo and Centrobin in early mitosis primes centrosome asymmetry

PLoS Biol. 2020 Aug 6;18(8):e3000762. doi: 10.1371/journal.pbio.3000762. eCollection 2020 Aug.

Abstract

Centrosomes, the main microtubule organizing centers (MTOCs) of metazoan cells, contain an older "mother" and a younger "daughter" centriole. Stem cells either inherit the mother or daughter-centriole-containing centrosome, providing a possible mechanism for biased delivery of cell fate determinants. However, the mechanisms regulating centrosome asymmetry and biased centrosome segregation are unclear. Using 3D-structured illumination microscopy (3D-SIM) and live-cell imaging, we show in fly neural stem cells (neuroblasts) that the mitotic kinase Polo and its centriolar protein substrate Centrobin (Cnb) accumulate on the daughter centriole during mitosis, thereby generating molecularly distinct mother and daughter centrioles before interphase. Cnb's asymmetric localization, potentially involving a direct relocalization mechanism, is regulated by Polo-mediated phosphorylation, whereas Polo's daughter centriole enrichment requires both Wdr62 and Cnb. Based on optogenetic protein mislocalization experiments, we propose that the establishment of centriole asymmetry in mitosis primes biased interphase MTOC activity, necessary for correct spindle orientation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Centrioles / metabolism*
  • Centrioles / ultrastructure
  • Centrosome / metabolism*
  • Centrosome / ultrastructure
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Interphase
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mitosis*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Optogenetics / methods
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction

Substances

  • Bacterial Proteins
  • Cell Cycle Proteins
  • Cnb protein, Drosophila
  • Drosophila Proteins
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Wdr62 protein, Drosophila
  • enhanced green fluorescent protein
  • red fluorescent protein
  • yellow fluorescent protein, Bacteria
  • Green Fluorescent Proteins
  • polo protein, Drosophila
  • Protein-Serine-Threonine Kinases