Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation |
| |
Authors: | Köttgen Michael Benzing Thomas Simmen Thomas Tauber Robert Buchholz Björn Feliciangeli Sylvain Huber Tobias B Schermer Bernhard Kramer-Zucker Albrecht Höpker Katja Simmen Katia Carmine Tschucke Christoph Carl Sandford Richard Kim Emily Thomas Gary Walz Gerd |
| |
Institution: | Michael Köttgen, Thomas Benzing, Thomas Simmen, Robert Tauber, Björn Buchholz, Sylvain Feliciangeli, Tobias B Huber, Bernhard Schermer, Albrecht Kramer-Zucker, Katja Höpker, Katia Carmine Simmen, Christoph Carl Tschucke, Richard Sandford, Emily Kim, Gary Thomas, and Gerd Walz |
| |
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. |
| |
Keywords: | PACS polycystin-2 TRPP2 |
本文献已被 PubMed 等数据库收录! |
|