The N-terminal extracellular domain is required for polycystin-1-dependent channel activity

Victor Babich, Wei Zhong Zeng, Byung Il Yeh, Oxana Ibraghimov-Beskrovnaya, Yiqiang Cai, Stefan Somlo, Chou Long Huang

Research output: Contribution to journalArticle

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Abstract

Autosomal dominant polycystic kidney disease (PKD) is caused by mutation of polycystin-1 or polycystin-2. Polycystin-2 is a Ca2+-permeable cation channel. Polycystin-1 is an integral membrane protein of less defined function. The N-terminal extracellular region of polycystin-1 contains potential motifs for protein and carbohydrate interaction. We now report that expression of polycystin-1 alone in Chinese hamster ovary (CHO) cells and in PKD2-null cells can confer Ca2+-permeable non-selective cation currents. Co-expression of a loss-of-function mutant of polycystin-2 in CHO cells does not reduce polycystin-1-dependent channel activity. A polycystin-1 mutant lacking ∼2900 amino acids of the extracellular region is targeted to the cell surface but does not produce current. Extracellular application of antibodies against the immunoglobulin-like PKD domains reduces polycystin-1-dependent current. These results support the hypothesis that polycystin-1 is a surface membrane receptor that transduces the signal via changes in ionic currents.

Original languageEnglish (US)
Pages (from-to)25582-25589
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number24
DOIs
StatePublished - Jun 11 2004

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Cricetulus
Cations
Ovary
Protein Interaction Domains and Motifs
Autosomal Dominant Polycystic Kidney
Polycystic Kidney Diseases
Null Lymphocytes
polycystic kidney disease 1 protein
Immunoglobulins
Membrane Proteins
Cells
Carbohydrates
Membranes
Amino Acids
Mutation
Antibodies
polycystic kidney disease 2 protein
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Babich, V., Zeng, W. Z., Yeh, B. I., Ibraghimov-Beskrovnaya, O., Cai, Y., Somlo, S., & Huang, C. L. (2004). The N-terminal extracellular domain is required for polycystin-1-dependent channel activity. Journal of Biological Chemistry, 279(24), 25582-25589. https://doi.org/10.1074/jbc.M402829200

The N-terminal extracellular domain is required for polycystin-1-dependent channel activity. / Babich, Victor; Zeng, Wei Zhong; Yeh, Byung Il; Ibraghimov-Beskrovnaya, Oxana; Cai, Yiqiang; Somlo, Stefan; Huang, Chou Long.

In: Journal of Biological Chemistry, Vol. 279, No. 24, 11.06.2004, p. 25582-25589.

Research output: Contribution to journalArticle

Babich, V, Zeng, WZ, Yeh, BI, Ibraghimov-Beskrovnaya, O, Cai, Y, Somlo, S & Huang, CL 2004, 'The N-terminal extracellular domain is required for polycystin-1-dependent channel activity', Journal of Biological Chemistry, vol. 279, no. 24, pp. 25582-25589. https://doi.org/10.1074/jbc.M402829200
Babich V, Zeng WZ, Yeh BI, Ibraghimov-Beskrovnaya O, Cai Y, Somlo S et al. The N-terminal extracellular domain is required for polycystin-1-dependent channel activity. Journal of Biological Chemistry. 2004 Jun 11;279(24):25582-25589. https://doi.org/10.1074/jbc.M402829200
Babich, Victor ; Zeng, Wei Zhong ; Yeh, Byung Il ; Ibraghimov-Beskrovnaya, Oxana ; Cai, Yiqiang ; Somlo, Stefan ; Huang, Chou Long. / The N-terminal extracellular domain is required for polycystin-1-dependent channel activity. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 24. pp. 25582-25589.
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