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

TitlePhospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation.
Publication TypeJournal Article
Year of Publication2017
AuthorsAguilera-Gomez, A, Zacharogianni, M, van Oorschot, MM, Genau, H, Grond, R, Veenendaal, T, Sinsimer, KS, Gavis, ER, Behrends, C, Rabouille, C
JournalCell Rep
Volume20
Issue4
Pagination935-948
Date Published2017 Jul 25
ISSN2211-1247
KeywordsAmino Acids, Animals, Carrier Proteins, Cytoplasmic Granules, Drosophila, Drosophila Proteins, Immunoprecipitation, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, Vesicular Transport Proteins
Abstract

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.

DOI10.1016/j.celrep.2017.06.042
Alternate JournalCell Rep
PubMed ID28746877