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Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation

Koettgen M, Benzing T, Simmen T, Tauber R, Buchholz B, Feliciangeli S, Huber TB, Schermer B, Kramer-Zucker A, Höpker K, Simmen KC, Tschucke CC, Sandford R, Kim E, Thomas G, Walz G (2005)

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Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2005

Journal

Publisher: WILEY

Book Volume: 24

Pages Range: 705-716

Journal Issue: 4

DOI: 10.1038/sj.emboj.7600566

Abstract

The trafficking of ion channels to the plasma membrane is tightly controlled to ensure the proper regulation of intracellular ion homeostasis and signal transduction. Mutations of polycystin- 2, a member of the TRP family of cation channels, cause autosomal dominant polycystic kidney disease, a disorder characterized by renal cysts and progressive renal failure. Polycystin- 2 functions as a calcium- permeable nonselective cation channel; however, it is disputed whether polycystin- 2 resides and acts at the plasma membrane or endoplasmic reticulum ( ER). We show that the subcellular localization and function of polycystin- 2 are directed by phosphofurin acidic cluster sorting protein ( PACS)- 1 and PACS- 2, two adaptor proteins that recognize an acidic cluster in the carboxy- terminal domain of polycystin- 2. Binding to these adaptor proteins is regulated by the phosphorylation of polycystin- 2 by the protein kinase casein kinase 2, required for the routing of polycystin- 2 between ER, Golgi and plasma membrane compartments. Our paradigm that polycystin- 2 is sorted to and active at both ER and plasma membrane reconciles the previously incongruent views of its localization and function. Furthermore, PACS proteins may represent a novel molecular mechanism for ion channel trafficking, directing acidic cluster- containing ion channels to distinct subcellular compartments.

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How to cite

APA:

Koettgen, M., Benzing, T., Simmen, T., Tauber, R., Buchholz, B., Feliciangeli, S.,... Walz, G. (2005). Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO Journal, 24(4), 705-716. https://doi.org/10.1038/sj.emboj.7600566

MLA:

Koettgen, Michael, et al. "Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation." EMBO Journal 24.4 (2005): 705-716.

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