Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2013-09-01Keywords
AnimalsCilia
Cysts
Disease Models, Animal
Genotype
Mice
Mice, Knockout
Mutation
Phenotype
Polycystic Kidney, Autosomal Dominant
TRPP Cation Channels
Molecular Genetics
Metadata
Show full item recordAbstract
Kidney cysts occur following inactivation of polycystins in otherwise intact cilia or following complete removal of cilia by inactivation of intraflagellar transport-related proteins. We investigated the mechanisms of cyst formation in these two distinct processes by combining conditional inactivation of polycystins with concomitant ablation of cilia in developing and adult kidney and liver. We found that loss of intact cilia suppressed cyst growth following inactivation of polycystins and that the severity of cystic disease was directly related to the length of time between the initial loss of the polycystin proteins and the subsequent involution of cilia. This cilia-dependent cyst growth was not explained by activation of the MAPK/ERK, mTOR or cAMP pathways and is likely to be distinct from the mechanism of cyst growth following complete loss of cilia. These data establish the existence of a new pathway defined by polycystin-dependent inhibition and cilia-dependent activation that promotes rapid cyst growth.Source
Nat Genet. 2013 Sep;45(9):1004-12. doi: 10.1038/ng.2715. Epub 2013 Jul 28. Link to article on publisher's siteDOI
10.1038/ng.2715Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30318PubMed ID
23892607Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ng.2715