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[Regulation of osmolyte transporter gene expression by tonicity]
M Takenaka1, A Yamauchi, E Imai
1First Department of Medicine, Osaka University School of Medicine.
Abstract:
In response to exposure to hypertonic environment, cells accumulate small organic solutes termed osmolytes that protect them from the adverse effects of hypertonicity. Some osmolytes (myo-inositol, betaine and taurine) are accumulated by specific transporters. Those transporters have been cloned by expression cloning techniques. Transcription of osmolyte transporters is induced by hypertonicity. In situ hybridization reveals the localization of the Na+/myo-inositol cotransporter and the betaine transporter (BGT1) mRNAs in the kidney. The BGT1 gene was cloned and its 5' flanking region has been characterized A 13 bp tonicity responsive enhancer (TONE) has been identified. Analysis of transgenic mice harboring a 5' flanking region of the BGT1 gene, that included TONE, showed that it provides inducible reporter expression in kidney medulla.
Insights
Cells protect themselves from hypertonic environments by accumulating osmolytes like myo-inositol and betaine using specific transporters. This study identified a tonicity-responsive enhancer (TONE) in the betaine transporter gene (BGT1) that regulates its expression in the kidney.
Area of Science:
- Cell biology
- Molecular biology
- Physiology
Background:
- Cells accumulate osmolytes (e.g., myo-inositol, betaine, taurine) to counteract hypertonic stress.
- Osmolyte accumulation is mediated by specific transporters, whose transcription is induced by hypertonicity.
- Kidney plays a crucial role in osmotic balance and osmolyte transport.
Purpose of the Study:
- To investigate the transcriptional regulation of osmolyte transporters in response to hypertonicity.
- To identify and characterize regulatory elements within the betaine transporter (BGT1) gene.
- To confirm the functional role of identified regulatory elements in vivo.
Main Methods:
- Expression cloning of osmolyte transporters.
- In situ hybridization to determine mRNA localization of transporters in the kidney.
- Gene cloning and 5' flanking region characterization of the BGT1 gene.
- Analysis of transgenic mice carrying the BGT1 gene's 5' flanking region.
Main Results:
- Specific transporters for myo-inositol, betaine, and taurine were cloned.
- Na+/myo-inositol cotransporter and betaine transporter (BGT1) mRNAs were localized to the kidney.
- A 13 bp tonicity-responsive enhancer (TONE) was identified in the 5' flanking region of the BGT1 gene.
- Transgenic mice demonstrated inducible reporter expression in the kidney medulla driven by the BGT1 5' flanking region containing TONE.
Conclusions:
- Hypertonicity induces the transcription of osmolyte transporters.
- The identified TONE element is a key regulator of BGT1 gene expression in the kidney medulla.
- This provides a molecular mechanism for kidney adaptation to hypertonic environments.