A Naturally Occurring Isoform Inhibits Parathyroid Hormone Receptor Trafficking and Signaling
2011

A New Isoform of the Parathyroid Hormone Receptor Affects Signaling

publication 10 minutes Evidence: moderate

Author Information

Author(s): Alonso Verónica, Ardura Juan A, Wang Bin, Sneddon W Bruce, Friedman Peter A

Primary Institution: University of Pittsburgh School of Medicine

Hypothesis

Does the Δe14-PTHR isoform impair the signaling and trafficking of the parathyroid hormone receptor (PTHR)?

Conclusion

The Δe14-PTHR isoform reduces PTHR signaling and causes PTH resistance by impairing receptor trafficking and expression.

Supporting Evidence

  • Δe14-PTHR was detected in human kidney and buccal epithelial cells.
  • Δe14-PTHR displayed impaired trafficking and accumulated in the endoplasmic reticulum.
  • Signaling and activation of cAMP and ERK by Δe14-PTHR was significantly decreased compared with PTHR.
  • Cells cotransfected with both receptors exhibited reduced PTHR cell membrane expression.

Takeaway

There is a new version of a receptor that helps control calcium in our bodies, and this version doesn't work well, making it harder for our bodies to respond to a hormone that helps manage calcium levels.

Methodology

The study involved characterizing the Δe14-PTHR isoform through various cellular and molecular biology techniques, including transfection, immunoblotting, and confocal microscopy.

Limitations

The study primarily focuses on in vitro models, which may not fully replicate in vivo conditions.

Participant Demographics

The study used renal proximal tubule cells isolated from normal human subjects.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1002/jbmr.167

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