Reg1 and Snf1 regulate stress-induced relocalization of protein phosphatase-1 to cytoplasmic granules.


Journal

The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646

Informations de publication

Date de publication:
08 2021
Historique:
revised: 22 02 2021
received: 02 12 2020
accepted: 03 03 2021
pubmed: 9 3 2021
medline: 8 9 2021
entrez: 8 3 2021
Statut: ppublish

Résumé

The compartmentalization of cellular function is achieved largely through the existence of membrane-bound organelles. However, recent work suggests a novel mechanism of compartmentalization mediated by membraneless structures that have liquid droplet-like properties and arise through phase separation. Cytoplasmic stress granules (SGs) are the best characterized and are induced by various stressors including arsenite, heat shock, and glucose deprivation. Current models suggest that SGs play an important role in protein homeostasis by mediating reversible translation attenuation. Protein phosphatase-1 (PP1) is a central cellular regulator responsible for most serine/threonine dephosphorylation. Here, we show that upon arsenite stress, PP1's catalytic subunit Glc7 relocalizes to punctate cytoplasmic granules. This altered localization requires PP1's recently described maturation pathway mediated by the multifunctional ATPase Cdc48 and PP1's regulatory subunit Ypi1. Glc7 relocalization is mediated by its regulatory subunit Reg1 and its target Snf1, the AMP-dependent protein kinase. Surprisingly, Glc7 granules are highly specific to arsenite and appear distinct from canonical SGs. Arsenite induces potent translational inhibition, and translational recovery is strongly dependent on Glc7, but independent of Glc7's well-established role in regulating eIF2α. These results suggest a novel form of stress-induced cytoplasmic granule and a new mode of translational control by Glc7.

Identifiants

pubmed: 33682330
doi: 10.1111/febs.15802
pmc: PMC8373691
mid: NIHMS1708410
doi:

Substances chimiques

Saccharomyces cerevisiae Proteins 0
SNF1-related protein kinases EC 2.7.1.-
Protein Serine-Threonine Kinases EC 2.7.11.1
Protein Phosphatase 1 EC 3.1.3.16
REG1 protein, S cerevisiae EC 3.1.3.16

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

4833-4848

Subventions

Organisme : NIH HHS
ID : DP5 OD019800
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM135337
Pays : United States

Informations de copyright

© 2021 Federation of European Biochemical Societies.

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Auteurs

Helena Maria Schnell (HM)

Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Marco Jochem (M)

Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Yagmur Micoogullari (Y)

Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Claire Louise Riggs (CL)

Department of Rheumatology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Pavel Ivanov (P)

Department of Rheumatology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Hendrik Welsch (H)

Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Rini Ravindran (R)

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.

Paul Anderson (P)

Department of Rheumatology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Lucy Christina Robinson (LC)

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.

Kelly Tatchell (K)

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.

John Hanna (J)

Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

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Classifications MeSH