VDAC3 and Mps1 negatively regulate ciliogenesis

Cell Cycle. 2013 Mar 1;12(5):849-58. doi: 10.4161/cc.23824. Epub 2013 Feb 6.

Abstract

Centrosomes serve to organize new centrioles in cycling cells, whereas in quiescent cells they assemble primary cilia. We have recently shown that the mitochondrial porin VDAC3 is also a centrosomal protein that is predominantly associated with the mother centriole and modulates centriole assembly by recruiting Mps1 to centrosomes. Here, we show that depletion of VDAC3 causes inappropriate ciliogenesis in cycling cells, while expression of GFP-VDAC3 suppresses ciliogenesis in quiescent cells. Mps1 also negatively regulates ciliogenesis, and the inappropriate ciliogenesis caused by VDAC3 depletion can be bypassed by targeting Mps1 to centrosomes independently of VDAC3. Thus, our data show that a VDAC3-Mps1 module at the centrosome promotes ciliary disassembly during cell cycle entry and suppresses cilia assembly in proliferating cells. Our data also suggests that VDAC3 might be a link between mitochondrial dysfunction and ciliopathies in mammalian cells.

Keywords: Mps1; VDAC; basal body; centrosome; ciliogenesis; primary cilia; quiescence.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Centrosome / metabolism
  • Cilia / metabolism*
  • Humans
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins / metabolism*
  • Organogenesis*
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport
  • Protein-Tyrosine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Serum / metabolism
  • Voltage-Dependent Anion Channels / metabolism*

Substances

  • Cell Cycle Proteins
  • Mitochondrial Membrane Transport Proteins
  • RNA, Small Interfering
  • VDAC3 protein, human
  • Voltage-Dependent Anion Channels
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • TTK protein, human