Journal article
A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability
- De Bellis, Manuela Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari “Aldo Moro,” 70126 Bari, Italy
- Pisani, Francesco Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari “Aldo Moro,” 70126 Bari, Italy
- Mola, Maria Grazia Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari “Aldo Moro,” 70126 Bari, Italy
- Basco, Davide Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland
- Catalano, Francesco M. Sarcone Hospital, 70038 Terlizzi, Bari, Italy
- Nicchia, Grazia Paola Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari “Aldo Moro,” 70126 Bari, Italy
- Svelto, Maria Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari “Aldo Moro,” 70126 Bari, Italy
- Frigeri, Antonio Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari “Aldo Moro,” 70126 Bari, Italy
Published in:
- Molecular Biology of the Cell. - American Society for Cell Biology (ASCB). - 2014, vol. 25, no. 4, p. 470-480
English
Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue. Here we report the identification and functional analysis of an alternatively spliced transcript of human AQP4, AQP4-Δ4, that lacks exon 4. In transfected cells AQP4-Δ4 is mainly retained in the endoplasmic reticulum and shows no water transport properties. When AQP4-Δ4 is transfected into cells stably expressing functional AQP4, the surface expression of the full-length protein is reduced. Furthermore, the water transport activity of the cotransfectants is diminished in comparison to transfectants expressing only AQP4. The observed down-regulation of both the expression and water channel activity of AQP4 is likely to originate from a dominant-negative effect caused by heterodimerization between AQP4 and AQP4-Δ4, which was detected in coimmunoprecipitation studies. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein and is physiologically associated with different types of skeletal muscles. The expression of AQP4-Δ4 may represent a new regulatory mechanism through which the cell-surface expression and therefore the activity of AQP4 can be physiologically modulated.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1091/mbc.e13-06-0331
- ISSN 1059-1524
- Persistent URL
- https://sonar.ch/global/documents/151043
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