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Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
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Signaling diversity enabled by Rap1-regulated plasma membrane ERK with distinct temporal dynamics.
Jeremiah Keyes1, Ambhighainath Ganesan2, Olivia Molinar-Inglis1
1Department of Pharmacology, University of California San Diego, La Jolla, United States.
Elife
|May 27, 2020
Summary
Specific temporal regulation of extracellular-signal regulated kinase (ERK) activity controls cellular responses. New biosensors reveal sustained ERK activity at the plasma membrane, contrasting with transient cytoplasmic and nuclear activity, impacting cell morphology.
Area of Science:
- Cellular signaling
- Molecular biology
- Biochemistry
Background:
- Extracellular-signal regulated kinase (ERK) pathways mediate diverse cellular responses.
- Signaling specificity is proposed to arise from precise temporal control of ERK activity.
- Understanding ERK regulation across subcellular compartments is crucial for deciphering signaling specificity.
Purpose of the Study:
- To develop and utilize advanced Förster Resonance Energy Transfer (FRET)-based biosensors for measuring spatiotemporal ERK activity.
- To investigate the subcellular localization and temporal dynamics of ERK activation in response to epidermal growth factor (EGF).
- To elucidate the role of localized ERK activity in controlling cellular processes.
Main Methods:
- Creation of a suite of improved FRET-based ERK biosensors engineered for specific subcellular targeting.
- Application of these biosensors to monitor ERK activity dynamics in real-time within different cellular compartments.
- Investigating the involvement of Rap1 in EGF-induced plasma membrane ERK activation.
Main Results:
- EGF stimulation results in sustained ERK activity localized near the plasma membrane.
- ERK activity in the cytoplasm and nucleus exhibits transient dynamics following EGF stimulation.
- EGF-induced plasma membrane ERK activation involves Rap1 and modulates cell morphology and membrane protrusion.
Conclusions:
- Spatial and temporal regulation of ERK activity are integrated mechanisms for achieving signaling specificity.
- Localized ERK signaling at the plasma membrane plays a critical role in mediating cellular responses to external stimuli.
- The developed FRET biosensors provide a powerful tool for dissecting complex signaling events in specific subcellular locations.
Keywords:
EGFERKPC12Rap1biochemistrycell biologychemical biologynonesignal transductionspatiotemporalMore Related Videos
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