Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation

Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): Angelica Aguilera-Gomez, Margarita Zacharogianni, Marinke M. van Oorschot, Heide Genau, Rianne Grond, Tineke Veenendaal, Kristina S. Sinsimer, Elisabeth A. Gavis, Christian Behrends, Catherine Rabouille
Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein.

Graphical abstract

Teaser

Aguilera-Gomez et al. show that, although stress granules appear similar, the mode of their formation depends on the cellular stress. Contrary to arsenite treatment, the RNA-binding protein Rasputin needs to be phosphorylated and bound to the ERES scaffold Sec16 to lead to the formation of stress granules upon amino acid starvation.


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