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Primary cilia regulate mTORC1 activity and cell size through Lkb1

Christopher Boehlke1, Fruzsina Kotsis, Vishal Patel

  • 1Renal Unit, Department of Medicine, University Medical Center, Albert-Ludwig-University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.

Nature Cell Biology
|October 26, 2010
PubMed

Insights

Cilia sense cell flow to control cell size by regulating the mTOR pathway. This study reveals cilia

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • The mechanistic target of rapamycin (mTOR) pathway regulates cell size, with its deregulation implicated in diseases like polycystic kidney disease (PKD).
  • Cilia, sensory organelles, are crucial for sensing environmental cues, and their dysfunction is linked to PKD, suggesting a potential role in cellular regulation.
  • The integration of external signals by the mTOR pathway and its precise translation into cellular responses remain incompletely understood.

Purpose of the Study:

  • To investigate the role of cilia in regulating the mTOR pathway and cell size control.
  • To elucidate the molecular mechanisms by which cilia influence mTOR signaling and cellular homeostasis.

Main Methods:

  • Ablation of cilia in transgenic mice to assess effects on cell size.
  • In vitro analysis of cilia bending induced by fluid flow to study mTOR downregulation.
  • Investigation of the involvement of Lkb1, AMPK, calcium transients, and Akt in cilia-mediated cell-size regulation.

Main Results:

  • Cilia ablation led to enlarged cells in transgenic mice, indicating a role for cilia in preventing excessive cell growth.
  • Cilia bending, induced by fluid flow, is essential for mTOR downregulation and maintaining normal cell size.
  • Cilia-mediated cell-size regulation is independent of flow-induced calcium transients and Akt, but relies on Lkb1 localization within the cilium and subsequent AMPK phosphorylation at the basal body.

Conclusions:

  • Cilia play a critical role in regulating mTOR signaling and controlling cell size.
  • The cilium-basal body compartment acts as a specific site for Lkb1 signaling activation in response to fluid flow.
  • Understanding cilia-mTOR interactions provides insights into cellular homeostasis and potential therapeutic targets for diseases like PKD.

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