Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease
TLDR
The existence of a new pathway defined by polycystin-dependent inhibition and cilia-dependent activation that promotes rapid cyst growth is established that is not explained by activation of the MAPK/ERK, mTOR or cAMP pathways.Abstract:
Stefan Somlo and colleagues show that loss of intact cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease (ADPKD). They further show that the severity of cystic disease in these models is directly related to the length of time between the initial loss of polycystins and the subsequent involution of cilia, implicating a cilia-dependent cyst growth–promoting pathway in the pathogenesis of ADPKD.read more
Citations
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Journal ArticleDOI
Polycystic kidney disease.
Carsten Bergmann,Lisa M. Guay-Woodford,Peter C. Harris,Shigeo Horie,Dorien J.M. Peters,Vicente E. Torres +5 more
TL;DR: An overview of the current knowledge of PKD and its treatment can be found in this paper, where the authors provide an overview of existing knowledge about the pathogenesis and treatment of polycystic kidney disease.
Journal ArticleDOI
Primary Cilia Are Not Calcium-Responsive Mechanosensors
Markus Delling,Artur A. Indzhykulian,Xu Liu,Yaqiao Li,T. Xie,David P. Corey,David E. Clapham +6 more
TL;DR: It is concluded that mechanosensation, if it originates in primary cilia, is not via calcium signalling, and cilia-specific Ca2+ influxes were not observed in physiological or even highly supraphysiological levels of fluid flow.
Journal ArticleDOI
Establishing and regulating the composition of cilia for signal transduction.
Maxence V. Nachury,David U. Mick +1 more
TL;DR: Cilia, and primary cilia in particular, are important signalling organelles with established roles in odorant, light and Hedgehog morphogen signal transduction and are enriched in signalling receptors and effectors and in specific lipids.
Journal ArticleDOI
Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease.
TL;DR: An improved understanding of aberrant downstream pathways in ADPKD, such as proliferation/secretion-related signaling, energy metabolism, and activated macrophages, in which cAMP and calcium changes may play a role, is leading to the identification of therapeutic targets.
Journal ArticleDOI
A polycystin-centric view of cyst formation and disease: the polycystins revisited
Albert C.M. Ong,Peter C. Harris +1 more
TL;DR: This review presents a current model of how the polycystin proteins function in health and disease and summarises the major findings in this area.
References
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A global double‐fluorescent Cre reporter mouse
Mandar Deepak Muzumdar,Bosiljka Tasic,Bosiljka Tasic,Kazunari Miyamichi,Kazunari Miyamichi,Ling Li,Ling Li,Liqun Luo,Liqun Luo +8 more
TL;DR: The mT/mG mouse as mentioned in this paper is a double-fluorescent Cre reporter mouse that expresses membrane-targeted tandem dimer tomato (mT) prior to Cre-mediated excision and membranetargeted green fluorescent protein (mG) after excision.
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Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells
Surya M. Nauli,Francis J. Alenghat,Ying Luo,Eric O. Williams,Peter M. Vassilev,Xiaogang Li,Andrew E. H. Elia,Weining Lu,Edward M. Brown,Stephen J. Quinn,Donald E. Ingber,Jing Zhou +11 more
TL;DR: PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway, suggesting loss or dysfunction of PC1 or PC2 may lead to polycystic kidney disease.
Journal ArticleDOI
Altered Neural Cell Fates and Medulloblastoma in Mouse patched Mutants
TL;DR: The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS).
Journal ArticleDOI
Patched1 Regulates Hedgehog Signaling at the Primary Cilium
TL;DR: The role of primary cilia in regulation of Patched1 (Ptc1), the receptor for Sonic Hedgehog (Shh), is investigated and it is found that Ptc1 localized to cilia and inhibited Smoothened (Smo) by preventing its accumulation within cilia.