title: 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 (Gαo) was characterized as an inducer of neuronal differentiation. However, its underlying molecular mechanisms have remained unclear to date, since the downstream effectors of Gαo are ambiguous.
  
  
  RESULTS
  A neurally differentiated embryonal carcinoma-derived protein (Necdin) was isolated as an interacting partner for Gαo 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 Gαo, compared to wild-type protein. Interestingly, Gαo did not interact with Gαi, despite high sequence homology between the two proteins. We subsequently analyzed whether Gαo modulates the cellular activities of Necdin. Notably, expression of Gαo significantly augmented Necdin-mediated cellular responses, such as proliferation and differentiation. Moreover, activation of type 1 cannabinoid receptor (CB1R), a Gi/oα-coupled receptor, augmented cell growth suppression, which was mediated by Gαo and Necdin in U87MG cells containing CB1R, Gαo, and Necdin as normal components.
  
  
  CONCLUSIONS
  These results collectively suggest that Necdin is a candidate downstream effector for Gαo. Our findings provide novel insights into the cellular roles of Gαo and its coupled receptor.
authors.forename: Hyunhee
authors.initials: H
authors.lastname: Ju
authors.forename: Sujin
authors.initials: S
authors.lastname: Lee
authors.forename: Sunghak
authors.initials: S
authors.lastname: Kang
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Sungho
authors.initials: S
authors.lastname: Ghil
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D043884:Receptor, Cannabinoid, CB1; C069766:necdin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go