Acetylation of the RhoA GEF Net1A controls its subcellular localization and activity
| Autor: | Arzu Ulu, Heather S. Carr, Eun Hyeon Song, Wonkyung Oh, Jeffrey A. Frost, Yan Zuo |
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| Rok vydání: | 2015 |
| Předmět: |
rac1 GTP-Binding Protein
rho GTP-Binding Proteins RHOA Nuclear Localization Signals Active Transport Cell Nucleus RAC1 Focal adhesion Mice Animals Humans Protein Isoforms NLS Cytoskeleton Cell Nucleus Mice Knockout Oncogene Proteins biology Cell Membrane Neuropeptides Acetylation Cell Biology Subcellular localization Cell biology biology.protein rhoA GTP-Binding Protein Nuclear localization sequence HeLa Cells Research Article |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Net1 isoform A (Net1A) is a RhoA GEF that is required for cell motility and invasion in multiple cancers. Nuclear localization of Net1A negatively regulates its activity, and we have recently shown that Rac1 stimulates Net1A relocalization to the plasma membrane to promote RhoA activation and cytoskeletal reorganization. However, mechanisms controlling the subcellular localization of Net1A are not well understood. Here, we show that Net1A contains two nuclear localization signal (NLS) sequences within its N-terminus and that residues surrounding the second NLS sequence are acetylated. Treatment of cells with deacetylase inhibitors or expression of active Rac1 promotes Net1A acetylation. Deacetylase inhibition is sufficient for Net1A relocalization outside the nucleus, and replacement of the N-terminal acetylation sites with arginine residues prevents cytoplasmic accumulation of Net1A caused by deacetylase inhibition or EGF stimulation. By contrast, replacement of these sites with glutamine residues is sufficient for Net1A relocalization, RhoA activation and downstream signaling. Moreover, the N-terminal acetylation sites are required for rescue of F-actin accumulation and focal adhesion maturation in Net1 knockout MEFs. These data indicate that Net1A acetylation regulates its subcellular localization to impact on RhoA activity and actin cytoskeletal organization. |
| Databáze: | OpenAIRE |
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