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Rescue of a nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutant by cell-penetrating peptides

Item Type:Article
Title:Rescue of a nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutant by cell-penetrating peptides
Creators Name:Oueslati, M. and Hermosilla, R. and Schoenenberger, E. and Oorschot, V. and Beyermann, M. and Wiesner, B. and Schmidt, A. and Klumperman, J. and Rosenthal, W. and Schuelein, R.
Abstract:Mutant membrane proteins are frequently retained in the early secretory pathway by a quality control system, thereby causing disease. An example are mutants of the vasopressin V(2) receptor (V(2)R) leading to nephrogenic diabetes insipidus. Transport-defective V(2)Rs fall into two classes: those retained exclusively in the endoplasmic reticulum (ER) and those reaching post-ER compartments such as the ER/Golgi intermediate compartment. Although numerous chemical or pharmacological chaperones that rescue the transport of ER-retained membrane proteins are known, substances acting specifically in post-ER compartments have not been described as yet. Using the L62P (ER-retained) and Y205C (reaching post-ER compartments) mutants of the V(2)R as a model, we show here that the cell-penetrating peptide penetratin and its synthetic analog KLAL rescue the transport of the Y205C mutant. In contrast, the location of the L62P mutant is not influenced by either peptide because the peptides are unable to enter the ER. We also show data indicating that the peptide-mediated transport rescue is associated with an increase in cytosolic Ca(2+) concentrations. Thus, we describe a new class of substances influencing protein transport specifically in post-ER compartments.
Keywords:Amino Acid Substitution, Calcium, Calcium Signaling, Carrier Proteins, Cell Line, Nephrogenic Diabetes Insipidus, Endoplasmic Reticulum, Golgi Apparatus, Molecular Chaperones, Missense Mutation, Protein Transport, Vasopressin Receptors
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:282
Number:28
Page Range:20676-20685
Date:13 July 2007
Official Publication:https://doi.org/10.1074/jbc.M611530200
PubMed:View item in PubMed

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