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A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability.
Journal article

A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability.

  • De Bellis M Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari "Aldo Moro," 70126 Bari, Italy Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland M. Sarcone Hospital, 70038 Terlizzi, Bari, Italy.
  • Pisani F
  • Mola MG
  • Basco D
  • Catalano F
  • Nicchia GP
  • Svelto M
  • Frigeri A
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  • 2013-12-21
Published in:
  • Molecular biology of the cell. - 2014
Alternative Splicing
Animals
Aquaporin 4
Astrocytes
Base Sequence
Biological Transport
Cerebellum
Exons
Frontal Lobe
Gastric Mucosa
Gene Expression
Gene Library
Genes, Dominant
HeLa Cells
Humans
Kidney
Models, Molecular
Molecular Sequence Data
Muscle, Skeletal
Organ Specificity
Primary Cell Culture
Protein Isoforms
Rats
Sequence Deletion
Water
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
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/78437
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