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

doi:10.1074/jbc.M402829200

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The N-terminal Extracellular Domain Is Required for Polycystin-1-dependent Channel Activity

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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 and Chou-Long Huang

The Journal of biological chemistry, Vol.279(24), pp.25582-25589

06/11/2004

DOI: 10.1074/jbc.M402829200

PMID: 15060061

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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.

Details

Title: Subtitle: The N-terminal Extracellular Domain Is Required for Polycystin-1-dependent Channel Activity
Creators: Victor Babich - The University of Texas Southwestern Medical Center
Wei-Zhong Zeng - The University of Texas Southwestern Medical Center
Byung-Il Yeh - The University of Texas Southwestern Medical Center
Oxana Ibraghimov-Beskrovnaya - Genzyme
Yiqiang Cai - Yale University
Stefan Somlo - Yale University
Chou-Long Huang - The University of Texas Southwestern Medical Center
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.279(24), pp.25582-25589
DOI: 10.1074/jbc.M402829200
PMID: 15060061
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 06/11/2004
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984359776902771

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