The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins

Martina Gentzsch, Liying Cui, April Mengos, Xiu-Bao D Chang, Jey Hsin Chen, John R. Riordan

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

ClC chloride channels are widely distributed in organisms across the evolutionary spectrum, and members of the mammalian family play crucial roles in cellular function and are mutated in several human diseases (Jentsch, T. J., Stein, V., Weinreich, F., and Zdebik, A. A. (2002) Physiol. Rev. 82, 503-568). Within the ClC-3, -4, -5 branch of the family that are intracellular channels, two alternatively spliced ClC-3 isoforms were recognized recently (Ogura, T., Furukawa, T., Toyozaki, T., Yamada, K., Zheng, Y. J., Katayama, Y., Nakaya, H., and Inagaki, N. (2002) FASEB J. 16, 863-865). ClC-3A resides in late endosomes where it serves as an anion shunt during acidification. We show here that the ClC-3B PDZ-binding isoform resides in the Golgi where it co-localizes with a small amount of the other known PDZ-binding chloride channel, CFTR (cystic fibrosis transmembrane conductance regulator). Both channel proteins bind the Golgi PDZ protein, GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein). Interestingly, however, when overexpressed, GOPC, which is thought to influence traffic in the endocytic/secretory pathway, causes a large reduction in the amounts of both channels, probably by leading them to the degradative end of this pathway. ClC-3B as well as CFTR also binds EBP50 (ERM-binding phosphoprotein 50) and PDZK1, which are concentrated at the plasma membrane. However, only PDZK1 was found to promote interaction between the two channels, perhaps because they were able to bind to two different PDZ domains in PDZK1. Thus while small portions of the populations of ClC-3B and CFTR may associate and co-localize, the bulk of the two populations reside in different organelles of cells where they are expressed heterologously or endogenously, and therefore their cellular functions are likely to be distinct and not primarily related.

Original languageEnglish (US)
Pages (from-to)6440-6449
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number8
DOIs
StatePublished - Feb 21 2003
Externally publishedYes

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Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Protein Isoforms
PDZ Domains
Amino Acid Motifs
Proteins
Acidification
Secretory Pathway
Endosomes
Phosphoproteins
Cell membranes
Organelles
Population
Anions
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry

Cite this

The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. / Gentzsch, Martina; Cui, Liying; Mengos, April; Chang, Xiu-Bao D; Chen, Jey Hsin; Riordan, John R.

In: Journal of Biological Chemistry, Vol. 278, No. 8, 21.02.2003, p. 6440-6449.

Research output: Contribution to journalArticle

Gentzsch, Martina ; Cui, Liying ; Mengos, April ; Chang, Xiu-Bao D ; Chen, Jey Hsin ; Riordan, John R. / The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 8. pp. 6440-6449.
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abstract = "ClC chloride channels are widely distributed in organisms across the evolutionary spectrum, and members of the mammalian family play crucial roles in cellular function and are mutated in several human diseases (Jentsch, T. J., Stein, V., Weinreich, F., and Zdebik, A. A. (2002) Physiol. Rev. 82, 503-568). Within the ClC-3, -4, -5 branch of the family that are intracellular channels, two alternatively spliced ClC-3 isoforms were recognized recently (Ogura, T., Furukawa, T., Toyozaki, T., Yamada, K., Zheng, Y. J., Katayama, Y., Nakaya, H., and Inagaki, N. (2002) FASEB J. 16, 863-865). ClC-3A resides in late endosomes where it serves as an anion shunt during acidification. We show here that the ClC-3B PDZ-binding isoform resides in the Golgi where it co-localizes with a small amount of the other known PDZ-binding chloride channel, CFTR (cystic fibrosis transmembrane conductance regulator). Both channel proteins bind the Golgi PDZ protein, GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein). Interestingly, however, when overexpressed, GOPC, which is thought to influence traffic in the endocytic/secretory pathway, causes a large reduction in the amounts of both channels, probably by leading them to the degradative end of this pathway. ClC-3B as well as CFTR also binds EBP50 (ERM-binding phosphoprotein 50) and PDZK1, which are concentrated at the plasma membrane. However, only PDZK1 was found to promote interaction between the two channels, perhaps because they were able to bind to two different PDZ domains in PDZK1. Thus while small portions of the populations of ClC-3B and CFTR may associate and co-localize, the bulk of the two populations reside in different organelles of cells where they are expressed heterologously or endogenously, and therefore their cellular functions are likely to be distinct and not primarily related.",
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AU - Cui, Liying

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AU - Chang, Xiu-Bao D

AU - Chen, Jey Hsin

AU - Riordan, John R.

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