Cilia downsize mTORC1

Wrighton, Katharine H.

doi:10.1038/nrm3019

Research Highlight
Published: 23 November 2010

Cell signalling

Cilia downsize mTORC1

Katharine H. Wrighton

Nature Reviews Molecular Cell Biology volume 11, page 821 (2010)Cite this article

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the bending of cilia by fluid flow activates the LKB1 ... pathway ... to downregulate mTOR signalling and inhibit cell size.

mTOR signalling is deregulated in polycystic kidney disease, in which mutations in ciliary proteins result in a failure to sense urine flow. As cells that line kidney cysts are enlarged, the authors postulated that cilia might regulate mTOR signalling and cell size. They first investigated whether loss of primary cilia affects cell size in vivo. Mouse kidneys with a mutation in the Kinesin-2 family member KIF3A lose cilia and have larger collecting duct cells than control animals, suggesting that primary cilia regulate cell size. The authors next generated a Madin–Darby canine kidney (MDCK) cell line in which KIF3A could be conditionally knocked down (termed KIF3A-i). These cells lack cilia and are larger than control cells when grown under fluid flow. Thus, loss of cilia increases cell size in vivo, and in vitro in the presence of flow.

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ORIGINAL RESEARCH PAPER

Boehlke, C. et al. Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nature Cell Biol. 12, 1115–1122 (2010) Article
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