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10.1038/ncb2117 http://scihub22266oqcxt.onion/10.1038/ncb2117 20972424!3390256!20972424     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Cell+Biol 2010 ; 12 (11): 1115-22 Nephropedia Template TP {{tp|p=20972424|t=2010. Primary cilia regulate mTORC1 activity and cell size through Lkb1 |pdf=|usr=}}{{20972424}} gab.com Text Primary cilia regulate mTORC1 activity and cell size through Lkb1 JO: Nat Cell Biol http://www.kidney.de/pget.php?&tw=1&pmid=20972424 #FOAvip 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. Twit Text FOAVip Primary cilia regulate mTORC1 activity and cell size through Lkb1 ????Nat Cell Biol http://www.kidney.de/pget.php?&tw=1&pmid=20972424 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=20972424 #FOAvip English Wikipedia <ref>{{Cite pmid|20972424}}</ref> Primary cilia regulate mTORC1 activity and cell size through Lkb1 #MMPMID20972424 Boehlke C; Kotsis F; Patel V; Braeg S; Voelker H; Bredt S; Beyer T; Janusch H; Hamann C; Godel M; Muller K; Herbst M; Hornung M; Doerken M; Kottgen M; Nitschke R; Igarashi P; Walz G; Kuehn EW Nat Cell Biol 2010[Nov]; 12 (11): 1115-22 PMID20972424show ga 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. |*Cell Size[MESH] |AMP-Activated Protein Kinases[MESH] |Animals[MESH] |Calcium/metabolism[MESH] |Cell Line[MESH] |Cilia/chemistry/*metabolism[MESH] |Dogs[MESH] |Kinesins/deficiency/metabolism[MESH] |Mechanistic Target of Rapamycin Complex 1[MESH] |Mice[MESH] |Mice, Transgenic[MESH] |Multiprotein Complexes[MESH] |Phosphorylation[MESH] |Protein Serine-Threonine Kinases/*metabolism[MESH] |Proteins/*metabolism[MESH] |Signal Transduction[MESH]Primary cilia regulate mTORC1 activity and cell size through Lkb1 (epmc).pdf DeepDyve Pubget Overpricing