期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 11, 页码 2057-2069出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.160341
关键词
S1P; SPC; Vimentin; ROCK; Phosphorylation; Sphingosine 1-phosphate; Sphingosylphosphorylcholine; migration; S1P(2); S1PR2; Intermediate filament
类别
资金
- Sigrid Juselius Foundation
- Liv och Halsa Foundation
- Academy of Finland
- Centre of Excellence in Cell Stress and Molecular Ageing (Abo Akademi University)
- Abo Akademi University
- Finnish Cultural Foundation
- Ida Montin Foundation
- K. Albin Johansson Foundation
- Tor, Joe and Pentti Borg Foundation
- Arvid and Greta Olin Foundation
- Receptor Research Program (Abo Akademi University)
- Receptor Research Program (University of Turku)
- Grants-in-Aid for Scientific Research [15K08324] Funding Source: KAKEN
The sphingolipids, sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), can induce or inhibit cellular migration. The intermediate filament protein vimentin is an inducer of migration and a marker for epithelial-mesenchymal transition. Given that keratin intermediate filaments are regulated by SPC, with consequences for cell motility, we wanted to determine whether vimentin is also regulated by sphingolipid signalling and whether it is a determinant for sphingolipid-mediated functions. In cancer cells where S1P and SPC inhibited migration, we observed that S1P and SPC induced phosphorylation of vimentin on S71, leading to a corresponding reorganization of vimentin filaments. These effects were sphingolipid-signalling-dependent, because inhibition of either the S1P2 receptor (also known as S1PR2) or its downstream effector Rho-associated kinase (ROCK, for which there are two isoforms ROCK1 and ROCK2) nullified the sphingolipid-induced effects on vimentin organization and S71 phosphorylation. Furthermore, the anti-migratory effect of S1P and SPC could be prevented by expressing S71-phosphorylation-deficient vimentin. In addition, we demonstrated, by using wild-type and vimentin-knockout mouse embryonic fibroblasts, that the sphingolipid-mediated inhibition of migration is dependent on vimentin. These results imply that this newly discovered sphingolipid-vimentin signalling axis exerts brake-and-throttle functions in the regulation of cell migration.
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