| First Author | Ju H | Year | 2014 |
| Journal | Cell Commun Signal | Volume | 12 |
| Pages | 39 | PubMed ID | 25012566 |
| Mgi Jnum | J:320702 | Mgi Id | MGI:6873022 |
| Doi | 10.1186/s12964-014-0039-9 | Citation | Ju H, et al. (2014) The alpha subunit of Go modulates cell proliferation and differentiation through interactions with Necdin. Cell Commun Signal 12:39 |
| abstractText | BACKGROUND: Heterotrimeric GTP-binding proteins (G-proteins) play an important role in mediating signal transduction generated by neurotransmitters or hormones. Go, a member of the Gi/Go subfamily, is the most abundant G-protein found in the brain. Recently, the alpha subunit of Go (Galphao) was characterized as an inducer of neuronal differentiation. However, its underlying molecular mechanisms have remained unclear to date, since the downstream effectors of Galphao are ambiguous. RESULTS: A neurally differentiated embryonal carcinoma-derived protein (Necdin) was isolated as an interacting partner for Galphao from a mouse brain cDNA library using yeast two-hybrid screening. Interactions between the proteins were confirmed with several affinity binding assays, both in vitro and in vivo. Necdin interacted directly and preferentially with activated Galphao, compared to wild-type protein. Interestingly, Galphao did not interact with Galphai, despite high sequence homology between the two proteins. We subsequently analyzed whether Galphao modulates the cellular activities of Necdin. Notably, expression of Galphao significantly augmented Necdin-mediated cellular responses, such as proliferation and differentiation. Moreover, activation of type 1 cannabinoid receptor (CB1R), a Gi/oalpha-coupled receptor, augmented cell growth suppression, which was mediated by Galphao and Necdin in U87MG cells containing CB1R, Galphao, and Necdin as normal components. CONCLUSIONS: These results collectively suggest that Necdin is a candidate downstream effector for Galphao. Our findings provide novel insights into the cellular roles of Galphao and its coupled receptor. |
