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The TRPP Signaling Module: TRPP2/Polycystin-1 and TRPP2/PKD1L1

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TRP Channels in Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

TRPP ion channels assemble with polycystin-1 family proteins into receptor-channel complexes. TRPP2–Polycystin-1 is required to coordinate renal three-dimensional tissue organization, whereas TRPP2–PKD1L1 is essential for establishment of left–right asymmetry during early embryonic development. The availability of orthologous and heterologous animal models made it feasible not only to characterize the function of single genes, but also to combine gene deficiencies and/or gene overexpression to establish molecular interdependencies. Canonical and noncanonical Wnt signaling have been associated with polycystic kidney disease. Furthermore, PRKCSH and SEC63 have been implicated in TRPP/polycystin protein maturation. Putative targets for therapeutic agents have set the stage for clinical intervention studies. The purpose of this review is to critically summarize recent in vivo evidence and to highlight inconsistencies that should be resolved if an accurate understanding of TRPP channels and polycystins is to be achieved. It is hoped that a deeper understanding of associated phenotypes will help to design rational therapies for autosomal dominant polycystic kidney disease.

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Acknowledgments

The author would like to thank Michael Köttgen for helpful ­discussions. He apologizes to those whose work could not be cited due to space limitations. Funding was awarded by the Deutsche Forschungsgemeinschaft (KFO 201) and the Excellence Initiative of the German Federal and State Governments (GSC-4, Spemann Graduate School).

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Authors and Affiliations

  1. Renal Division, Department of Medicine, University Medical Centre Freiburg, Freiburg, Germany

    Alexis Hofherr

  2. Spemann Graduate School of Biology and Medicine (SGBM) and Faculty of Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany

    Alexis Hofherr

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  1. Alexis Hofherr
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Correspondence to Alexis Hofherr .

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Editors and Affiliations

  1. , Transfusion Services, Monmouth Medical Center, Second Avenue 300, Long Branch, 07740, New Jersey, USA

    Arpad Szallasi

  2. Medical and Health Science Center, Department of Physiology, University of Debrecen, Nagyerdei Krt. 98, Debrecen, 4032, Hungary

    Tamás Bíró

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Hofherr, A. (2012). The TRPP Signaling Module: TRPP2/Polycystin-1 and TRPP2/PKD1L1. In: Szallasi, A., Bíró, T. (eds) TRP Channels in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-077-9_10

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  • DOI: https://doi.org/10.1007/978-1-62703-077-9_10

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-076-2

  • Online ISBN: 978-1-62703-077-9

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