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Biochim Biophys Acta. 2015 Jul;1853(7):1725-37. doi: 10.1016/j.bbamcr.2015.03.015. Epub 2015 Mar 31.

5'-AMP-activated protein kinase alpha regulates stress granule biogenesis.

Author information

1
Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.
2
Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada. Electronic address: ursula.stochaj@mcgill.ca.

Abstract

Stress granule (SG) assembly represents a conserved eukaryotic defense strategy against various insults. Although essential for the ability to cope with deleterious conditions, the signaling pathways controlling SG formation are not fully understood. The energy sensor AMP-activated protein kinase (AMPK) is critical for the cellular stress response. Human cells produce two AMPK catalytic α-subunits with not only partially overlapping, but also unique functions. Here, we provide direct support for structural and functional links between AMPK-α isoforms and SGs. As such, several stressors promote SG association of AMPK-α2, but not AMPK-α1. Multiple lines of evidence link AMPK activity to SG biogenesis. First, pharmacological kinase inhibition interfered with SG formation. Second, AMPK-α knockdown combined with in-depth quantitative SG analysis revealed isoform-specific changes of SG characteristics. Third, overexpression of mutant α-subunits further substantiated that AMPK regulates SG parameters. Finally, we identified the SG-nucleating protein G3BP1 as an AMPK-α2 binding partner. This interaction is stimulated by stress and notably occurs in SGs. Collectively, our data define the master metabolic regulator AMPK as a novel SG constituent that also controls their biogenesis.

KEYWORDS:

5′-AMP-activated protein kinase; Apoptosis; Oxidative stress; Quantitative microscopy; Signaling; Stress granules

PMID:
25840010
DOI:
10.1016/j.bbamcr.2015.03.015
[Indexed for MEDLINE]
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