Aurora-A recruitment and centrosomal maturation are regulated by a Golgi-activated pool of Src during G2

Nat Commun. 2016 May 31:7:11727. doi: 10.1038/ncomms11727.

Abstract

The Golgi apparatus is composed of stacks of cisternae laterally connected by tubules to form a ribbon-like structure. At the onset of mitosis, the Golgi ribbon is broken down into discrete stacks, which then undergo further fragmentation. This ribbon cleavage is required for G2/M transition, which thus indicates that a 'Golgi mitotic checkpoint' couples Golgi inheritance with cell cycle transition. We previously showed that the Golgi-checkpoint regulates the centrosomal recruitment of the mitotic kinase Aurora-A; however, how the Golgi unlinking regulates this recruitment was unknown. Here we show that, in G2, Aurora-A recruitment is promoted by activated Src at the Golgi. Our data provide evidence that Src and Aurora-A interact upon Golgi ribbon fragmentation; Src phosphorylates Aurora-A at tyrosine 148 and this specific phosphorylation is required for Aurora-A localization at the centrosomes. This process, pivotal for centrosome maturation, is a fundamental prerequisite for proper spindle formation and chromosome segregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A / genetics
  • Aurora Kinase A / physiology*
  • CSK Tyrosine-Protein Kinase
  • Centrosome / physiology*
  • Chromosome Segregation / physiology
  • G2 Phase / physiology*
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Indoles / pharmacology
  • Phosphorylation
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Rats
  • S Phase / drug effects
  • Sulfonamides / pharmacology
  • Thymidine / pharmacology
  • Tyrosine / metabolism
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / physiology*

Substances

  • Indoles
  • RNA, Small Interfering
  • SU 6656
  • Sulfonamides
  • Tyrosine
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • AURKA protein, human
  • Aurora Kinase A
  • Thymidine