| First Author | Nagashima S | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 20107 |
| PubMed ID | 31882856 | Mgi Jnum | J:307194 |
| Mgi Id | MGI:6719546 | Doi | 10.1038/s41598-019-56559-9 |
| Citation | Huang J, et al. (2019) Critical role of CRAG, a splicing variant of centaurin-gamma3/AGAP3, in ELK1-dependent SRF activation at PML bodies. Sci Rep 9(1):20107 |
| abstractText | CRMP-5-associated GTPase (CRAG), a short splicing variant of centaurin-gamma3/AGAP3, is predominantly expressed in the developing brain. We previously demonstrated that CRAG, but not centaurin-gamma3, translocates to the nucleus and activates the serum response factor (SRF)-c-Fos pathway in cultured neuronal cells. However, the physiological relevance of CRAG in vivo is unknown. Here, we found that CRAG/centaurin-gamma3-knockout mice showed intensively suppressed kainic acid-induced c-fos expression in the hippocampus. Analyses of molecular mechanisms underlying CRAG-mediated SRF activation revealed that CRAG has an essential role in GTPase activity, interacts with ELK1 (a co-activator of SRF), and activates SRF in an ELK1-dependent manner. Furthermore, CRAG and ELK1 interact with promyelocytic leukaemia bodies through SUMO-interacting motifs, which is required for SRF activation. These results suggest that CRAG plays a critical role in ELK1-dependent SRF-c-fos activation at promyelocytic leukaemia bodies in the developing brain. |
