title: FUS/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress.
abstract: FUsed in Sarcoma/Translocated in LipoSarcoma (FUS/TLS or FUS) has been linked to several biological processes involving DNA and RNA processing, and has been associated with multiple diseases, including myxoid liposarcoma and amyotrophic lateral sclerosis (ALS). ALS-associated mutations cause FUS to associate with stalled translational complexes called stress granules under conditions of stress. However, little is known regarding the normal role of endogenous (non-disease linked) FUS in cellular stress response. Here, we demonstrate that endogenous FUS exerts a robust response to hyperosmolar stress induced by sorbitol. Hyperosmolar stress causes an immediate re-distribution of nuclear FUS to the cytoplasm, where it incorporates into stress granules. The redistribution of FUS to the cytoplasm is modulated by methyltransferase activity, whereas the inhibition of methyltransferase activity does not affect the incorporation of FUS into stress granules. The response to hyperosmolar stress is specific, since endogenous FUS does not redistribute to the cytoplasm in response to sodium arsenite, hydrogen peroxide, thapsigargin, or heat shock, all of which induce stress granule assembly. Intriguingly, cells with reduced expression of FUS exhibit a loss of cell viability in response to sorbitol, indicating a prosurvival role for endogenous FUS in the cellular response to hyperosmolar stress.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Reddy Ranjith K
authors.initials: RR
authors.lastname: Sama
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Ward
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Kaushansky
authors.forename: Nathan
authors.initials: N
authors.lastname: Lemay
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ishigaki
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Urano
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Bosco
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology*; D008745:Methylation / Q000187:drug effects; D051379:Mice; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D013012:Sorbitol / Q000494:pharmacology / Q000633:toxicity; D013312:Stress, Physiological / Q000187:drug effects*
chemical_list: D006982:Hypertonic Solutions; D034702:RNA-Binding Protein FUS; D013012:Sorbitol