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AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic
- Source :
- PLoS ONE, Vol 10, Iss 5, p e0128013 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- The cell surface proteome controls numerous cellular functions including cell migration and adhesion, intercellular communication and nutrient uptake. Cell surface proteins are controlled by acute changes in protein abundance at the plasma membrane through regulation of endocytosis and recycling (endomembrane traffic). Many cellular signals regulate endomembrane traffic, including metabolic signaling; however, the extent to which the cell surface proteome is controlled by acute regulation of endomembrane traffic under various conditions remains incompletely understood. AMP-activated protein kinase (AMPK) is a key metabolic sensor that is activated upon reduced cellular energy availability. AMPK activation alters the endomembrane traffic of a few specific proteins, as part of an adaptive response to increase energy intake and reduce energy expenditure. How increased AMPK activity during energy stress may globally regulate the cell surface proteome is not well understood. To study how AMPK may regulate the cell surface proteome, we used cell-impermeable biotinylation to selectively purify cell surface proteins under various conditions. Using ESI-MS/MS, we found that acute (90 min) treatment with the AMPK activator A-769662 elicits broad control of the cell surface abundance of diverse proteins. In particular, A-769662 treatment depleted from the cell surface proteins with functions in cell migration and adhesion. To complement our mass spectrometry results, we used other methods to show that A-769662 treatment results in impaired cell migration. Further, A-769662 treatment reduced the cell surface abundance of β1-integrin, a key cell migration protein, and AMPK gene silencing prevented this effect. While the control of the cell surface abundance of various proteins by A-769662 treatment was broad, it was also selective, as this treatment did not change the cell surface abundance of the transferrin receptor. Hence, the cell surface proteome is subject to acute regulation by treatment with A-769662, at least some of which is mediated by the metabolic sensor AMPK.
- Subjects :
- Integrins
Proteome
Cell
Integrin
lcsh:Medicine
Thiophenes
AMP-Activated Protein Kinases
Mass Spectrometry
Cell Line
Cell Movement
Cell Adhesion
medicine
Humans
Biotinylation
Endomembrane system
Cell adhesion
Protein kinase A
lcsh:Science
Multidisciplinary
biology
Biphenyl Compounds
Cell Membrane
lcsh:R
AMPK
Cell biology
Protein Transport
medicine.anatomical_structure
Gene Expression Regulation
Pyrones
biology.protein
lcsh:Q
Intracellular
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....05b9c88bf255bbd1186e61658e928616