Next Article in Journal
Saponins as Modulators of the Blood Coagulation System and Perspectives Regarding Their Use in the Prevention of Venous Thromboembolic Incidents
Next Article in Special Issue
Methods for Studying Endocytotic Pathways of Herpesvirus Encoded G Protein-Coupled Receptors
Previous Article in Journal
Naphthalenes and Quinolines by Domino Reactions of Morita–Baylis–Hillman Acetates
Previous Article in Special Issue
Natural Compounds as Guides for the Discovery of Drugs Targeting G-Protein-Coupled Receptors
Article

AGS3 and Gαi3 Are Concomitantly Upregulated as Part of the Spindle Orientation Complex during Differentiation of Human Neural Progenitor Cells

1
Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China
2
State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China
*
Author to whom correspondence should be addressed.
Present address: School of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, Victoria 3083, Australia.
Academic Editor: Sławomir Filipek
Molecules 2020, 25(21), 5169; https://doi.org/10.3390/molecules25215169
Received: 29 September 2020 / Revised: 29 October 2020 / Accepted: 3 November 2020 / Published: 6 November 2020
(This article belongs to the Special Issue G Protein-Coupled Receptors)
Adult neurogenesis is modulated by many Gi-coupled receptors but the precise mechanism remains elusive. A key step for maintaining the population of neural stem cells in the adult is asymmetric cell division (ACD), a process which entails the formation of two evolutionarily conserved protein complexes that establish the cell polarity and spindle orientation. Since ACD is extremely difficult to monitor in stratified tissues such as the vertebrate brain, we employed human neural progenitor cell lines to examine the regulation of the polarity and spindle orientation complexes during neuronal differentiation. Several components of the spindle orientation complex, but not those of the polarity complex, were upregulated upon differentiation of ENStem-A and ReNcell VM neural progenitor cells. Increased expression of nuclear mitotic apparatus (NuMA), Gαi subunit, and activators of G protein signaling (AGS3 and LGN) coincided with the appearance of a neuronal marker (β-III tubulin) and the concomitant loss of neural progenitor cell markers (nestin and Sox-2). Co-immunoprecipitation assays demonstrated that both Gαi3 and NuMA were associated with AGS3 in differentiated ENStem-A cells. Interestingly, AGS3 appeared to preferentially interact with Gαi3 in ENStem-A cells, and this specificity for Gαi3 was recapitulated in co-immunoprecipitation experiments using HEK293 cells transiently overexpressing GST-tagged AGS3 and different Gαi subunits. Moreover, the binding of Gαi3 to AGS3 was suppressed by GTPγS and pertussis toxin. Disruption of AGS3/Gαi3 interaction by pertussis toxin indicates that AGS3 may recognize the same site on the Gα subunit as G protein-coupled receptors. Regulatory mechanisms controlling the formation of spindle orientation complex may provide novel means to manipulate ACD which in turn may have an impact on neurogenesis. View Full-Text
Keywords: AGS3; G protein; LGN; neurogenesis; NuMA; Ric-8A AGS3; G protein; LGN; neurogenesis; NuMA; Ric-8A
Show Figures

Figure 1

MDPI and ACS Style

Yip, J.L.K.; Lee, M.M.K.; Leung, C.C.Y.; Tse, M.K.; Cheung, A.S.T.; Wong, Y.H. AGS3 and Gαi3 Are Concomitantly Upregulated as Part of the Spindle Orientation Complex during Differentiation of Human Neural Progenitor Cells. Molecules 2020, 25, 5169. https://doi.org/10.3390/molecules25215169

AMA Style

Yip JLK, Lee MMK, Leung CCY, Tse MK, Cheung AST, Wong YH. AGS3 and Gαi3 Are Concomitantly Upregulated as Part of the Spindle Orientation Complex during Differentiation of Human Neural Progenitor Cells. Molecules. 2020; 25(21):5169. https://doi.org/10.3390/molecules25215169

Chicago/Turabian Style

Yip, Jackson L.K., Maggie M.K. Lee, Crystal C.Y. Leung, Man K. Tse, Annie S.T. Cheung, and Yung H. Wong. 2020. "AGS3 and Gαi3 Are Concomitantly Upregulated as Part of the Spindle Orientation Complex during Differentiation of Human Neural Progenitor Cells" Molecules 25, no. 21: 5169. https://doi.org/10.3390/molecules25215169

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop