Polycystin-2 is an intracellular calcium release channel
Peter Koulen1, Yiqiang Cai, Lin Geng
1Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Nature Cell Biology
|February 21, 2002
Summary
Polycystin-2 acts as a calcium-activated channel in the endoplasmic reticulum, crucial for intracellular calcium release. Its dysfunction causes polycystic kidney disease due to disrupted calcium signaling.
Area of Science:
- Molecular Biology
- Cell Biology
- Nephrology
Background:
- Polycystin-2 is the protein product of the gene mutated in autosomal dominant polycystic kidney disease (ADPKD).
- It belongs to the transient receptor potential (TRP) channel superfamily and is abundant in the endoplasmic reticulum (ER) membrane.
Purpose of the Study:
- To investigate the function of polycystin-2 as an ion channel.
- To elucidate the role of polycystin-2 in intracellular calcium signaling and its relation to ADPKD.
Main Methods:
- Single channel electrophysiological studies.
- Epithelial cell culture and overexpression models.
- Analysis of intracellular calcium release signals.
Main Results:
- Polycystin-2 functions as a high-conductance, calcium-activated channel in the ER membrane.
- It is permeable to divalent cations.
- Overexpression of polycystin-2 enhances intracellular calcium release, which is abolished by mutations or truncation.
Conclusions:
- Polycystin-2 acts as a calcium-activated intracellular calcium release channel in vivo.
- Polycystic kidney disease arises from the loss of regulated intracellular calcium release signaling mediated by polycystin-2.
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