Adducin-1 is essential for spindle pole integrity through its interaction with TPX2

EMBO Rep. 2018 Aug;19(8):e45607. doi: 10.15252/embr.201745607. Epub 2018 Jun 19.

Abstract

Bipolar spindle assembly is necessary to ensure the proper progression of cell division. Loss of spindle pole integrity leads to multipolar spindles and aberrant chromosomal segregation. However, the mechanism underlying the maintenance of spindle pole integrity remains unclear. In this study, we show that the actin-binding protein adducin-1 (ADD1) is phosphorylated at S726 during mitosis. S726-phosphorylated ADD1 localizes to centrosomes, wherein it organizes into a rosette-like structure at the pericentriolar material. ADD1 depletion causes centriole splitting and therefore results in multipolar spindles during mitosis, which can be restored by re-expression of ADD1 and the phosphomimetic S726D mutant but not by the S726A mutant. Moreover, the phosphorylation of ADD1 at S726 is crucial for its interaction with TPX2, which is essential for spindle pole integrity. Together, our findings unveil a novel function of ADD1 in maintaining spindle pole integrity through its interaction with TPX2.

Keywords: TPX2; adducin; centrosome; mitosis; spindle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calmodulin-Binding Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Centrioles / metabolism
  • Centrosome / metabolism
  • Gene Deletion
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Mitosis
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Binding
  • Spindle Poles / metabolism*

Substances

  • Calmodulin-Binding Proteins
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • TPX2 protein, human
  • adducin
  • Phosphoserine