Michael Köttgen

TL;DR: This study shows using functional assays that human ATP-binding cassette, subfamily G, 2 (ABCG2), encoded by the ABCG2 gene contained in this region, is a hitherto unknown urate efflux transporter and supports the common disease-common variant hypothesis in the etiology of gout.

TL;DR: It is found that TRPV4, like TRPP2, is an essential component of the ciliary mechanosensor, and the concept that defective ciliary flow sensing constitutes the fundamental mechanism of cystogenesis is challenged.

TL;DR: It is demonstrated now that nephrin is a signaling molecule, which stimulates mitogen-activated protein kinases, which enhances Nephrin-induced signaling is greatly enhanced by podocin, which binds to the cytoplasmic tail of nephin.

TL;DR: It is shown that ablation of cilia in transgenic mice results in enlarged cells when compared with control animals, and the cilium-basal body compartment is identified as a spatially restricted activation site for Lkb1 signalling.

Abstract: 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.