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Novel subcellular locations and functions for secretory pathway Ca2+/Mn2+-ATPases
Tony D Southall1, Selim Terhzaz, Pablo Cabrero
1Division of Molecular Genetics, Anderson College Complex, University of Glasgow, Glasgow, United Kingdom.
Physiological Genomics
|April 13, 2006
Summary
The Drosophila SPCA gene (SPoCk) encodes three isoforms with unique roles in calcium (Ca2+) and manganese (Mn2+) transport. These isoforms localize to the ER, Golgi, and peroxisomes, impacting Ca2+ signaling and transport in renal tubules.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Genetics
Background:
- Secretory pathway Ca2+/Mn2+-ATPases (SPCAs) maintain cellular Ca2+ and Mn2+ homeostasis.
- All previously identified SPCAs were localized to the Golgi apparatus.
Purpose of the Study:
- To identify and characterize novel Ca2+-ATPases in Drosophila.
- To investigate the subcellular localization and function of SPoCk isoforms.
- To understand the role of SPoCk in Ca2+ handling and transport.
Main Methods:
- In silico screening for novel Ca2+-ATPases.
- Identification and characterization of SPoCk isoforms.
- Subcellular localization studies using Drosophila cells and Malpighian tubules.
- Overexpression and interfering RNA (RNAi) studies.
- Analysis of cytosolic Ca2+ handling and neuropeptide-stimulated diuresis.
Main Results:
- The Drosophila SPCA gene (SPoCk) encodes three isoforms with distinct subcellular localizations: ER, Golgi, and peroxisomes.
- The peroxisome-associated SPoCk isoform exhibits sexually dimorphic expression.
- Organelle-specific SPoCk isoforms differentially affect cytosolic Ca2+ handling and transport.
- SPoCk isoforms are crucial for inositol trisphosphate-mediated Ca2+ signaling, diuresis, and Ca2+ storage/transport in renal tubules.
- RNAi against SPoCk disrupted Ca2+ signaling and abolished neuropeptide-stimulated diuresis.
Conclusions:
- SPoCk plays a critical role in maintaining Ca2+ homeostasis in Drosophila.
- SPoCk isoforms contribute to both Ca2+ signaling and bulk Ca2+ transport/storage in epithelial cells.
- The diverse localization and functions of SPoCk isoforms highlight their importance in cellular physiology.
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