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Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
Published on: February 21, 2016
Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2
Karla M Knobel1, Erik M Peden, Maureen M Barr
1University of Wisconsin School of Pharmacy, Division of Pharmaceutical Sciences; 777 Highland Avenue Madison WI 53705, USA.
Experimental Cell Research
|November 27, 2007
Summary
Transient Receptor Potential Polycystin-2 (TRPP2) channel targeting to cellular compartments requires its transmembrane region and cytosolic termini. Human TRPP2 partially rescues C. elegans pkd-2 mutations, indicating functional homology.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- Transient Receptor Potential Polycystin-2 (TRPP2) channels are crucial for cellular function and are found in the endoplasmic reticulum and primary cilium.
- Mutations in human TRPP2 (PC-2) lead to autosomal dominant polycystic kidney disease (ADPKD).
- The C. elegans homolog, PKD-2, is essential for sensation in male-specific sensory neurons, localized to somatodendritic and ciliary compartments.
Purpose of the Study:
- To investigate the structure-function-localization relationships of TRPP2 channels in vivo.
- To identify the molecular determinants of PKD-2 subcellular targeting and function.
- To explore the functional conservation between human TRPP2 and its C. elegans homolog.
Main Methods:
- In vivo structure-function-localization studies in the model organism Caenorhabditis elegans.
- Analysis of PKD-2 localization and function in response to mutations affecting its domains.
- Heterologous expression of human TRPP2 (PC-2) in C. elegans to assess functional rescue of pkd-2 null mutants.
Main Results:
- The transmembrane region of PKD-2 is essential for its targeting to somatodendritic and ciliary compartments.
- Cytosolic termini of PKD-2 play a critical role in regulating its subcellular distribution and neuronal function.
- PKD-2 colocalizes with the OSM-9 TRP vanilloid (TRPV) channel in neuronal cell bodies, suggesting a functional partnership.
- Human TRPP2 (PC-2) partially rescues pkd-2 null mutant defects in C. elegans, despite not visibly localizing to cilia.
Conclusions:
- TRPP2 channel targeting and function are regulated by specific domains, including the transmembrane region and cytosolic termini.
- PKD-2 and TRP vanilloid channels may cooperate in sensory neuron function.
- Human TRPP2 and C. elegans PKD-2 are functional homologs, offering a model for studying TRPP2 channelopathies like ADPKD.
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