An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease

Schwake M, Friedrich T, Jentsch TJ (2001)
Journal of Biological Chemistry 276(15): 12049-12054.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
Download
OA 571.35 KB
Autor*in
Schwake, MichaelUniBi ; Friedrich, Thomas; Jentsch, Thomas J.
Abstract / Bemerkung
The ClC-5 chloride channel resides mainly in vesicles of the endocytotic pathway and contributes to their acidification. Its disruption in mice entails a broad defect in renal endocytosis and causes secondary changes in calciotropic hormone levels. Inactivating mutations in Dent's disease lead to proteinuria and kidney stones. Possibly by recycling, a small fraction of ClC-5 also reaches the plasma membrane. Here we identify a carboxyl-terminal internalization motif in ClC-5. It resembles the PY motif, which is crucial for the endocytosis and degradation of epithelial Na+ channels. Mutating this motif increases surface expression and currents about 2-fold. This is probably because of interactions with WW domains, because dominant negative mutants of the ubiquitin-protein ligase WWP2 increased surface expression and currents of ClC-5 only when its PY motif was intact. Stimulating endocytosis by expressing rab5 or its GTPase-deficient Q79L mutant decreased WT ClC-5 currents but did not affect channels with mutated motifs. Similarly, decreasing endocytosis by expressing the inactive S34N mutant of rab5 increased ClC-5 currents only if its PY-like motif was intact. Thus, the endocytosis of ClC-5, which itself is crucial for the endocytosis of other proteins, depends on the interaction of a carboxyl-terminal internalization signal with ubiquitin-protein ligases containing WW domains.
Erscheinungsjahr
2001
Zeitschriftentitel
Journal of Biological Chemistry
Band
276
Ausgabe
15
Seite(n)
12049-12054
ISSN
0021-9258
Page URI
https://pub.uni-bielefeld.de/record/2953363

Zitieren

Schwake M, Friedrich T, Jentsch TJ. An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease. Journal of Biological Chemistry. 2001;276(15):12049-12054.
Schwake, M., Friedrich, T., & Jentsch, T. J. (2001). An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease. Journal of Biological Chemistry, 276(15), 12049-12054. https://doi.org/10.1074/jbc.M010642200
Schwake, M., Friedrich, T., and Jentsch, T. J. (2001). An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease. Journal of Biological Chemistry 276, 12049-12054.
Schwake, M., Friedrich, T., & Jentsch, T.J., 2001. An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease. Journal of Biological Chemistry, 276(15), p 12049-12054.
M. Schwake, T. Friedrich, and T.J. Jentsch, “An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease”, Journal of Biological Chemistry, vol. 276, 2001, pp. 12049-12054.
Schwake, M., Friedrich, T., Jentsch, T.J.: An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease. Journal of Biological Chemistry. 276, 12049-12054 (2001).
Schwake, Michael, Friedrich, Thomas, and Jentsch, Thomas J. “An Internalization Signal in ClC-5, an Endosomal Cl−Channel Mutated in Dent's Disease”. Journal of Biological Chemistry 276.15 (2001): 12049-12054.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Creative Commons Namensnennung 4.0 International Public License (CC-BY 4.0):
Volltext(e)
Access Level
OA Open Access
Zuletzt Hochgeladen
2021-04-12T07:21:31Z
MD5 Prüfsumme
8b6e13b556d0f92d8b778229ef59afe5

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 11116157
PubMed | Europe PMC

Suchen in

Google Scholar