Journal article

A polycystin multiprotein complex constitutes a cholesterol-containing signalling microdomain in human kidney epithelia


Authors listRoitbak, Tamara; Surviladze, Zurab; Tikkanen, Ritva; Wandinger-Ness, Angela

Publication year2005

Pages29-38

JournalBiochemical Journal

Volume number392

ISSN0264-6021

eISSN1470-8728

DOI Linkhttps://doi.org/10.1042/BJ20050645

PublisherPortland Press


Abstract
Polycystins are plasma membrane proteins that are expressed in kidney epithelial cells and associated with the progression of ADPKD (autosomal dominant polycystic kidney disease). A polycystin multiprotein complex, including adherens junction proteins, is thought to play an important role in cell polarity and differentiation. Sucrose gradient analyses and immunoprecipitation studies of primary human kidney epithelial cells showed the polycystins and their associated proteins E-cadherin and beta-catenin distributed in a complex with the raft marker flotillin-2, but not caveolin-1, in high-density gradient fractions. The integrity of the polycystin multiprotein complex was sensitive to cholesterol depletion, as shown by cyclodextrin treatment of immunoprecipitated complexes. The overexpressed C-terminus of polycystin-1 retained the ability to associate with flotillin-2. Flotillin-2 was found to contain CRAC (cholesterol recognition/interaction amino acid) cholesterol-binding domains and to promote plasma membrane cholesterol recruitment. Based on co-association of signalling molecules, such as Src kinases and phosphatases, we propose that the polycystin multiprotein complex is embedded in a cholesterol-containing signalling microdomain specified by flotillin-2, which is distinct from classical light-buoyant-density, detergent-resistant domains.



Citation Styles

Harvard Citation styleRoitbak, T., Surviladze, Z., Tikkanen, R. and Wandinger-Ness, A. (2005) A polycystin multiprotein complex constitutes a cholesterol-containing signalling microdomain in human kidney epithelia, Biochemical Journal, 392, pp. 29-38. https://doi.org/10.1042/BJ20050645

APA Citation styleRoitbak, T., Surviladze, Z., Tikkanen, R., & Wandinger-Ness, A. (2005). A polycystin multiprotein complex constitutes a cholesterol-containing signalling microdomain in human kidney epithelia. Biochemical Journal. 392, 29-38. https://doi.org/10.1042/BJ20050645


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