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TRPP2 in Polycystic Kidney Disease

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Pathologies of Calcium Channels

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Abstract

Mutations in PKD1 (85 %) or PKD2 (15 %) account for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). The ADPKD proteins, polycystin-1 and polycystin-2 interact to form a receptor-ion channel complex which regulates tubular structure in the developing and adult kidney. Polycystin-2 (TRPP2) is the founding member of the Transient Receptor Potential Polycystic (TRPP) subfamily of non-selective ion channels. Considerable progress has been made in recent years to understand the structure and function of TRPP2 and its relevance to the pathogenesis of ADPKD. TRPP2 channels have been shown to reside in a number of different subcellular compartments regulating intracellular calcium levels as part of a complex with polycystin-1 and other channel proteins. Disturbed calcium signalling mediated by loss of TRPP2 or its interacting partner polycystin-1 is clearly an early event in the development of a cystic phenotype. Understanding the functional significance of disrupted calcium signalling and identifying affected downstream pathways may lead to the development of new therapeutic approaches in the treatment of ADPKD.

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  1. Kidney Genetics Group, Academic Nephrology Unit, The Henry Wellcome Laboratories for Medical Research, University of Sheffield Medical School, Sheffield, UK

    Andrew Streets & Albert Ong

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  2. Albert Ong
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  1. Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada

    Norbert Weiss

  2. Department of Neurophysiology and Pharmacology, Medical University Vienna, Vienna, Austria

    Alexandra Koschak

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Streets, A., Ong, A. (2014). TRPP2 in Polycystic Kidney Disease. In: Weiss, N., Koschak, A. (eds) Pathologies of Calcium Channels. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40282-1_24

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