2014 Jul 10;12(1):39. [Epub ahead of print]
The alpha subunit of Go modulates cell proliferation and differentiation through interactions with Necdin.
Abstract
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 (G¿o) was characterized as an inducer of neuronal differentiation. However, its underlying molecular mechanisms have remained unclear to date, since the downstream effectors of G¿o are ambiguous.ResultsA neurally differentiated embryonal carcinoma-derived protein (Necdin) was isolated as an interacting partner for G¿o 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 G¿o, compared to wild-type protein. Interestingly, G¿o did not interact with G¿i, despite high sequence homology between the two proteins. We subsequently analyzed whether G¿o modulates the cellular activities of Necdin. Notably, expression of G¿o significantly augmented Necdin-mediated cellular responses, such as proliferation and differentiation. Moreover, activation of type 1 cannabinoid receptor (CB1R), a Gi/o¿-coupled receptor, augmented cell growth suppression, which was mediated by G¿o and Necdin in U87MG cells containing CB1R, G¿o, and Necdin as normal components. Conclusions: These results collectively suggest that Necdin is a candidate downstream effector for G¿o. Our findings provide novel insights into the cellular roles of G¿o and its coupled receptor.
- PMID:
25012566
[PubMed – as supplied by publisher]
