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Published on: June 7, 2019
Illuminating compartmentalized AMPK signaling in single cells
Arnav Jhawar1, Kasey Parks1, Danielle L Schmitt1,2,3
1Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, U.S.A.
AMP-activated protein kinase (AMPK) regulates cellular energy. New reporters and actuators reveal its spatial and temporal activity, highlighting compartmentalized metabolic control.
Area of Science:
- Cellular Biology
- Metabolism
- Biochemistry
Background:
- AMP-activated protein kinase (AMPK) is a central regulator of cellular energy homeostasis.
- AMPK activation occurs via AMP binding and phosphorylation by kinases like LKB1 and CaMKK2, or independently by CaMKK2 through calcium signaling.
- Understanding AMPK's spatiotemporal activity is crucial for metabolic research.
Purpose of the Study:
- To review the evolution of genetically encoded kinase activity reporters for measuring AMPK activity in single cells.
- To discuss the application of genetic actuators for targeted AMPK inhibition.
- To highlight insights into AMPK regulation by upstream kinases, location, and signaling cues.
Main Methods:
- Utilized genetically encoded kinase activity reporters to measure spatial and temporal AMPK activity.
- Reviewed studies employing these reporters to investigate AMPK regulation.
- Discussed the use of genetic actuators, such as AMPK inhibitory peptides, for compartment-specific suppression.
Main Results:
- Genetically encoded reporters provide comprehensive measurements of AMPK activity in single cells.
- These tools have elucidated AMPK's dependence on upstream kinases, subcellular location, and specific signaling cues.
- Genetic actuators enable targeted modulation of AMPK activity within distinct cellular compartments.
Conclusions:
- AMPK is a key metabolic regulator with complex spatial and temporal signaling patterns.
- Evidence suggests significant compartmentalization of AMPK activity within the cell.
- Advances in reporter and actuator technologies offer powerful means to dissect AMPK signaling.
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