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Updated: Jun 21, 2026
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Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease
Published on: February 3, 2012
Polycystin-1 C-terminal cleavage is modulated by polycystin-2 expression
Claudia A Bertuccio1, Hannah C Chapin, Yiqiang Cai
1Departments of Cellular and Molecular Physiology, New Haven, Connecticut 06510, USA.
The Journal of Biological Chemistry
|June 4, 2009
Summary
Polycystin-2 (PC-2) influences polycystin-1 (PC-1) C-terminal tail (CTT) cleavage and nuclear entry. This process is independent of calcium signaling but regulated by PC-2
Area of Science:
- Molecular biology
- Genetics
- Cell biology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) results from mutations in PC-1 and PC-2 genes.
- PC-1 cleavage releases its C-terminal tail (CTT) into the nucleus.
- The role of PC-2 in PC-1 CTT processing is not fully understood.
Purpose of the Study:
- To investigate whether PC-2 influences the cleavage and nuclear translocation of PC-1 CTT.
- To determine if calcium signaling affects PC-1 CTT cleavage mediated by PC-2.
- To identify regions of PC-2 critical for modulating PC-1 CTT processing.
Main Methods:
- A quantitative cleavage assay using a PKDgalvp fusion protein was employed.
- Cells were cotransfected with PKDgalvp and PC-2.
- Intracellular calcium levels were manipulated using various agents.
- PC-2 C-terminal truncated mutants were generated and analyzed.
Main Results:
- Cotransfection with PC-2 increased luciferase activity and PC-1 CTT expression, confirming CTT cleavage and nuclear entry.
- PC-2's enhancement of CTT processing was independent of intracellular calcium concentrations.
- Specific sequences within the PC-2 C-terminal tail were identified as necessary for stimulating PC-1 CTT accumulation.
Conclusions:
- PC-2 influences and stabilizes the release of PC-1 CTT.
- The PC-1/PC-2 interaction in CTT processing is calcium-independent.
- This interaction suggests a novel signaling pathway modulated by PC-1 and PC-2.
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