Both G3BP1 and G3BP2 contribute to stress granule formation

Jan 3, 2013Genes to cells : devoted to molecular & cellular mechanisms

Both G3BP1 and G3BP2 help form stress granules

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Knockdowns of both G3BP1 and G3BP2 significantly reduced the number of stress granule-positive cells under arsenite exposure.

Cells exposed to environmental stresses like arsenite form stress granules (SGs) as a protective response.
G3BP1 is known to initiate SG assembly by forming multimers, while G3BP2 is a closely related protein involved in this process.
Single knockdown of G3BP1 or G3BP2 partially reduced SG formation, but simultaneous knockdown of both greatly diminished it.
G3BP2 can form both homo-multimers and hetero-multimers with G3BP1, indicating a collaborative role in SG formation.
Overexpression of G3BP2 can induce SG formation independently of stress stimuli.

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Upon exposure to various environmental stresses such as arsenite, hypoxia, and heat shock, cells inhibit their translation and apoptosis and then repair stress-induced alterations, such as DNA damage and the accumulation of misfolded proteins. These types of stresses induce the formation of cytoplasmic RNA granules called stress granules (SGs). SGs are storage sites for the many mRNAs released from disassembled polysomes under these stress conditions and are essential for the selective translation of stress-inducible genes. Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer. In this study, we examined the role of G3BP2, a close relative of G3BP1, in SG formation. Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. G3BP2 formed a homo-multimer and a hetero-multimer with G3BP1. Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli. Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses.

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Both G3BP1 and G3BP2 contribute to stress granule formation

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