The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Primary cilia regulate mTORC1 activity and cell size through Lkb1
Open accessAbstract
The mTOR pathway is the central regulator of cell size. External signals from growth factors and nutrients converge on the mTORC1 multi-protein complex to modulate downstream targets, but how the different inputs are integrated and translated into specific cellular responses is incompletely understood. Deregulation of the mTOR pathway occurs in polycystic kidney disease (PKD), where cilia (filiform sensory organelles) fail to sense urine flow because of inherited mutations in ciliary proteins. We therefore investigated if cilia have a role in mTOR regulation. Here, we show that ablation of cilia in transgenic mice results in enlarged cells when compared with control animals. In vitro analysis demonstrated that bending of the cilia by flow is required for mTOR downregulation and cell-size control. Surprisingly, regulation of cell size by cilia is independent of flow-induced calcium transients, or Akt. However, the tumour-suppressor protein Lkb1 localises in the cilium, and flow results in increased AMPK phosphorylation at the basal body. Conversely, knockdown of Lkb1 prevents normal cell-size regulation under flow conditions. Our results demonstrate that the cilium regulates mTOR signalling and cell size, and identify the cilium-basal body compartment as a spatially restricted activation site for Lkb1 signalling.
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Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells
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Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action
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Cited by
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
Signaling through the Primary Cilium
Wheway, G., Nazlamova, L., & Hancock, J. T. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00008 · Cited by 483
Proteomics of Primary Cilia by Proximity Labeling
Mick, D. U., Rodrigues, R. B., Leib, R. D., Adams, C. M., Chien, A. S., Gygi, S. P., & Nachury, M. V. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.10.015 · Cited by 409
Functional interaction between autophagy and ciliogenesis
Pampliega, O., Orhon, I., Patel, B., Sridhar, S., Díaz-Carretero, A., Beau, I., Codogno, P., Satir, B. H., Satir, P., & Cuervo, A. M. (2013) · Nature · doi:10.1038/nature12639 · Cited by 424
Lloyd, A. C. (2013) · Cell · doi:10.1016/j.cell.2013.08.053 · Cited by 393
Metadata
- Authors
- Boehlke, C., Kotsis, F., Patel, V., Braeg, S., Voelker, H., Bredt, S., Beyer, T., Janusch, H., Hamann, C., Gödel, M., Müller, K., Herbst, M., Hornung, M., Doerken, M., Köttgen, M., Nitschke, R., Igarashi, P., Walz, G., & Kuehn, E. W.
- Venue
- Nature Cell Biology
- Published
- 2010-10-24
- Volume
- 12
- Issue
- 11
- Pages
- 1115-1122
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1978201430
- Cited by
- 388
- References
- 44
- FWCI
- 15.26
- Type
- journal article
- Language
- en
- Open access
- green
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- Boehlke, C., Kotsis, F., Patel, V., Braeg, S., Voelker, H., Bredt, S., Beyer, T., Janusch, H., Hamann, C., Gödel, M., Müller, K., Herbst, M., Hornung, M., Doerken, M., Köttgen, M., Nitschke, R., Igarashi, P., Walz, G., & Kuehn, E. W. (2010). Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nature Cell Biology. https://doi.org/10.1038/ncb2117
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