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Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
Cell fate decisions are specified by the dynamic ERK interactome
Alex von Kriegsheim1, Daniela Baiocchi1, Marc Birtwistle1
1Signalling and Proteomics Laboratory, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
Nature Cell Biology
|November 26, 2009
Summary
Sustained extracellular signal-regulated kinase (ERK) activation drives neuronal differentiation. Dynamic changes in ERK-interacting proteins reveal complex regulatory mechanisms, not a single switch, controlling this cell fate decision.
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- Extracellular signal-regulated kinase (ERK) is crucial for cellular functions, including cell fate decisions.
- In PC12 cells, sustained ERK activation, not transient, induces neuronal differentiation.
- Understanding the dynamic interactions of ERK proteins is key to deciphering differentiation mechanisms.
Purpose of the Study:
- To identify dynamic changes in ERK-interacting proteins during neuronal differentiation.
- To elucidate the regulatory mechanisms controlling the switch from transient to sustained ERK activation.
- To investigate how these protein interactions influence cell fate decisions.
Main Methods:
- Quantitative proteomics was employed to identify ERK-interacting proteins.
- PC12 cells were induced to differentiate to observe dynamic protein changes.
- Functional characterization of identified proteins and integration with mathematical modeling were performed.
Main Results:
- 284 ERK-interacting proteins were identified.
- 60 proteins altered their binding to ERK upon differentiation induction.
- These proteins regulate differentiation via signal duration, localization, feedback, and crosstalk with the Akt pathway.
Conclusions:
- ERK-mediated neuronal differentiation is controlled by distributed mechanisms, not a single switch.
- Dynamic interactions of ERK-associated proteins are critical for regulating signal duration and cell fate.
- This study reveals novel regulators of the ERK pathway involved in differentiation.
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