Related Experiment Video
Updated: Aug 15, 2026
Imaging Calcium in Drosophila at Egg Activation
Published on: August 6, 2016
The Ca(2+)-calmodulin-activated protein phosphatase calcineurin negatively regulates EGF receptor signaling in
Kathleen M C Sullivan1, Gerald M Rubin
1Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA. kmcs@uclink2.berkeley.edu
Abstract:
Calcineurin is a Ca(2+)-calmodulin-activated, Ser-Thr protein phosphatase that is essential for the translation of Ca(2+) signals into changes in cell function and development. We carried out a dominant modifier screen in the Drosophila eye using an activated form of the catalytic subunit to identify new targets, regulators, and functions of calcineurin. An examination of 70,000 mutagenized flies yielded nine specific complementation groups, four that enhanced and five that suppressed the activated calcineurin phenotype. The gene canB2, which encodes the essential regulatory subunit of calcineurin, was identified as a suppressor group, demonstrating that the screen was capable of identifying genes relevant to calcineurin function. We demonstrated that a second suppressor group was sprouty, a negative regulator of receptor tyrosine kinase signaling. Wing and eye phenotypes of ectopic activated calcineurin and genetic interactions with components of signaling pathways suggested a role for calcineurin in repressing Egf receptor/Ras signal transduction. On the basis of our results, we propose that calcineurin, upon activation by Ca(2+)-calmodulin, cooperates with other factors to negatively regulate Egf receptor signaling at the level of sprouty and the GTPase-activating protein Gap1.
Insights
Calcineurin, a key calcium-activated phosphatase, was studied in Drosophila. Researchers identified new calcineurin regulators, revealing its role in repressing EGF receptor signaling via Sprouty.
Area of Science:
- Molecular Biology
- Cell Signaling
- Genetics
Background:
- Calcineurin (CaN) is a crucial calcium- and calmodulin-dependent serine/threonine protein phosphatase.
- It mediates calcium ion (Ca2+) signaling, impacting cell function and development.
- Understanding CaN's targets and regulators is vital for deciphering cellular responses.
Purpose of the Study:
- To identify novel calcineurin targets, regulators, and functions using a genetic screen.
- To investigate the role of calcineurin in Drosophila melanogaster development and signaling pathways.
- To elucidate the molecular mechanisms by which calcineurin influences cellular processes.
Main Methods:
- A dominant modifier screen was performed in the Drosophila eye using an activated form of calcineurin's catalytic subunit.
- Approximately 70,000 mutagenized flies were examined to identify genetic interactions.
- Genetic analysis, including complementation groups and phenotypic characterization, was employed.
Main Results:
- Nine complementation groups were identified, with four enhancing and five suppressing the activated calcineurin phenotype.
- The gene canB2, encoding calcineurin's regulatory subunit, was found in a suppressor group.
- Sprouty, a negative regulator of receptor tyrosine kinase signaling, was identified as a suppressor, suggesting calcineurin's role in repressing EGF receptor/Ras signaling.
Conclusions:
- Calcineurin plays a role in negatively regulating EGF receptor signaling in Drosophila.
- The findings propose that activated calcineurin interacts with Sprouty and Gap1 to modulate this pathway.
- This study identifies new components and mechanisms involved in calcineurin-mediated cellular regulation.
Related Concept Videos
01:23Negative Regulator Molecules
02:54Canonical Wnt Signaling Pathway
01:41Non-Canonical Wnt Signaling Pathways
01:22Amplifying Signals via Enzymatic Cascade
01:22Activation and Inactivation of G Proteins
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...