Nek2 kinase displaces distal appendages from the mother centriole prior to mitosis

J Cell Biol. 2020 Mar 2;219(3):e201907136. doi: 10.1083/jcb.201907136.

Abstract

Distal appendages (DAs) of the mother centriole are essential for the initial steps of ciliogenesis in G1/G0 phase of the cell cycle. DAs are released from centrosomes in mitosis by an undefined mechanism. Here, we show that specific DAs lose their centrosomal localization at the G2/M transition in a manner that relies upon Nek2 kinase activity to ensure low DA levels at mitotic centrosomes. Overexpression of active Nek2A, but not kinase-dead Nek2A, prematurely displaced DAs from the interphase centrosomes of immortalized retina pigment epithelial (RPE1) cells. This dramatic impact was also observed in mammary epithelial cells with constitutively high levels of Nek2. Conversely, Nek2 knockout led to incomplete dissociation of DAs and cilia in mitosis. As a consequence, we observed the presence of a cilia remnant that promoted the asymmetric inheritance of ciliary signaling components and supported cilium reassembly after cell division. Together, our data establish Nek2 as an important kinase that regulates DAs before mitosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Centrioles / enzymology*
  • Centrioles / genetics
  • Cilia / enzymology*
  • Cilia / genetics
  • Epithelial Cells / enzymology*
  • Female
  • G2 Phase Cell Cycle Checkpoints
  • Hematopoietic Stem Cells / enzymology
  • Humans
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / enzymology
  • Mice
  • Microtubule Proteins / genetics
  • Microtubule Proteins / metabolism
  • Mitosis*
  • NIMA-Related Kinases / genetics
  • NIMA-Related Kinases / metabolism*
  • Protein Binding
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / enzymology*
  • Signal Transduction
  • Time Factors

Substances

  • CEP164 protein, human
  • Microtubule Proteins
  • NEK2 protein, human
  • NIMA-Related Kinases
  • Nek2 protein, mouse