The alpha subunit of Go modulates cell proliferation and differentiation through interactions with Necdin

Cell Communication and Signaling

Research

Sung-Soo Kim¹  Sujin Lee²  Sungho Ghil²  Hyunhee Ju²  Sunghak Kang² 

[1]Department of Anatomy, Ajou University, School of Medicine, 443-721, Suwon, Republic of Korea

[2]Department of Life Science, Kyonggi University, 443-760, Suwon, Republic of Korea

关键词: Cannabinoid;    E2F1;    G-protein coupled receptor;    Yeast two-hybrid;   

DOI  :  10.1186/s12964-014-0039-9

 received in 2014-01-27, accepted in 2014-06-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundHeterotrimeric 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.ResultsA 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.ConclusionsThese 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.

【 授权许可】

Unknown   
© Ju et al.; licensee Biomed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.