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Updated: Jul 21, 2026
07:26
Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
Published on: October 15, 2016
Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in
I Nemere1, M C Farach-Carson, B Rohe
1Department of Nutrition and Food Sciences, and Center for Integrated BioSystems, Utah State University, Logan, UT 84322-8700, USA. nemere@cc.usu.edu
Summary
The 1,25D(3)-MARRS protein, identical to ERp57, binds 1,25(OH)(2)D(3) and mediates rapid phosphate uptake in chick intestines. Its expression declines with age, correlating with reduced hormone response.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- The seco-steroid 1,25(OH)(2)D(3) regulates phosphate homeostasis.
- A membrane-associated protein mediates rapid responses to 1,25(OH)(2)D(3), distinct from nuclear receptors.
- The identity and function of this rapid-response protein were previously unclear.
Purpose of the Study:
- To clone and sequence the chicken cDNA for the 1,25D(3)-MARRS protein.
- To functionally characterize the 1,25D(3)-MARRS protein's role in 1,25(OH)(2)D(3) signaling.
- To investigate the protein's involvement in age-related changes in phosphate transport.
Main Methods:
- Ribozyme loss-of-function approach to reduce 1,25D(3)-MARRS protein levels.
- Cloning and sequencing of the chicken cDNA for 1,25D(3)-MARRS protein.
- Measurement of 1,25(OH)(2)D(3) binding to membrane proteins and nuclear receptors.
- Assessment of phosphate uptake in isolated intestinal cells and perfused duodena.
- Western blot analysis for protein kinase C activity and 1,25D(3)-MARRS protein levels.
- Quantitative analysis of 1,25D(3)-MARRS mRNA expression in relation to age.
Main Results:
- The cloned chicken cDNA encodes a protein identical to the multifunctional ERp57, designated 1,25D(3)-MARRS protein.
- Ribozyme-mediated reduction of 1,25D(3)-MARRS protein decreased specific membrane binding of 1,25(OH)(2)D(3) but not nuclear receptor binding.
- 1,25D(3)-MARRS protein levels correlated with 1,25(OH)(2)D(3)-dependent protein kinase C activity.
- Phosphate uptake stimulation by 1,25(OH)(2)D(3) was observed in young birds but diminished in older birds.
- Age-related decline in 1,25D(3)-MARRS mRNA levels was observed up to 1 year of age.
Conclusions:
- The 1,25D(3)-MARRS protein (ERp57) is a key mediator of rapid, membrane-associated 1,25(OH)(2)D(3) signaling in chick intestinal phosphate transport.
- The protein's function is distinct from the nuclear vitamin D receptor pathway.
- Age-dependent downregulation of 1,25D(3)-MARRS protein contributes to the decline in intestinal phosphate transport efficiency in older birds.
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