Cellular Stress Induces Nucleocytoplasmic Transport Deficits Independent of Stress Granules

Joni Vanneste; Thomas Vercruysse; Steven Boeynaems; Philip Van Damme; Dirk Daelemans; Ludo Van Den Bosch

doi:10.3390/biomedicines10051057

Cellular Stress Induces Nucleocytoplasmic Transport Deficits Independent of Stress Granules

Biomedicines. 2022 May 3;10(5):1057. doi: 10.3390/biomedicines10051057.

Authors

Joni Vanneste^{1

2}, Thomas Vercruysse³, Steven Boeynaems⁴, Philip Van Damme^{1

2

5}, Dirk Daelemans³, Ludo Van Den Bosch^{1

2}

Affiliations

¹ KU Leuven, Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), B-3000 Leuven, Belgium.
² VIB, Center for Brain and Disease Research, Laboratory of Neurobiology, B-3000 Leuven, Belgium.
³ KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium.
⁴ Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁵ Department of Neurology, University Hospitals Leuven, B-3000 Leuven, Belgium.

Abstract

Stress granules are non-membrane bound granules temporarily forming in the cytoplasm in response to stress. Proteins of the nucleocytoplasmic transport machinery were found in these stress granules and it was suggested that stress granules contribute to the nucleocytoplasmic transport defects in several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The aim of this study was to investigate whether there is a causal link between stress granule formation and nucleocytoplasmic transport deficits. Therefore, we uncoupled stress granule formation from cellular stress while studying nuclear import. This was carried out by preventing cells from assembling stress granules despite being subjected to cellular stress either by knocking down both G3BP1 and G3BP2 or by pharmacologically inhibiting stress granule formation. Conversely, we induced stress granules by overexpressing G3BP1 in the absence of cellular stress. In both conditions, nuclear import was not affected demonstrating that stress granule formation is not a direct cause of stress-induced nucleocytoplasmic transport deficits.

Keywords: amyotrophic lateral sclerosis; arsenite; neurodegeneration; nuclear import.

Grants and funding

This research was supported by VIB, KU Leuven (C1 and “Opening the Future” Fund), the “Fund for Scientific Research Flanders” (FWO-Vlaanderen), the Agency for Innovation by Science and Technology (IWT; SBO-iPSCAF), the Thierry Latran Foundation, the ‘Association Belge contre les Maladies neuro-Musculaires’ (ABMM) and the ALS Liga België (A Cure for ALS). J.V. is supported by a strategic basic research PhD fellowship awarded by FWO-Vlaanderen. S.B. acknowledges an EMBO Long Term Fellowship. P.V.D. holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders and the KU Leuven funds “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”.