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Published on: February 17, 2017
Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression
1Department of Pharmacology, Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093-0647, USA.
Nature
|May 15, 1998
Summary
Oscillations in inositol 1,4,5-trisphosphate (InsP3) and calcium levels control cellular responses. Rapid, repetitive InsP3 release maximizes gene expression, highlighting the importance of oscillatory signaling.
Area of Science:
- Cellular signaling
- Calcium dynamics
- Molecular biology
Background:
- Inositol 1,4,5-trisphosphate (InsP3) regulates intracellular calcium release.
- Calcium oscillations are crucial for various cellular functions.
- Controlling InsP3 levels spatially and temporally is key to understanding its downstream effects.
Purpose of the Study:
- To develop a method for controlled delivery and release of InsP3 in unpermeabilized cells.
- To investigate the role of InsP3 and calcium oscillations in regulating gene expression.
Main Methods:
- Synthesis of a membrane-permeant, caged InsP3 derivative.
- Delivery into intact cells and subsequent uncaging via UV illumination.
- Measurement of cytosolic free calcium spikes and gene expression (NFAT activation).
Main Results:
- A novel caged InsP3 derivative was synthesized and successfully delivered into cells.
- UV-induced uncaging generated InsP3 analogue, leading to calcium spikes and NFAT-mediated gene expression.
- Gene expression was maximized when InsP3 analogue was released in oscillations at approximately 1-minute intervals.
Conclusions:
- Oscillatory patterns of InsP3 and calcium signaling are critical for efficient gene expression.
- This caged InsP3 system provides a powerful tool for studying calcium signaling dynamics.
- Physiological rates of calcium oscillations optimize cellular responses like gene expression.
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