Imperial College London
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Emeritus ProfessorStephenFranks

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Emeritus Professor of Reproductive Endocrinology
 
 
 
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Contact

 

+44 (0)20 7594 2109s.franks Website

 
 
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Assistant

 

Miss Kiran Dosanjh +44 (0)20 7594 4217

 
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Location

 

5009Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sayers:2022:10.3389/fendo.2021.798866,
author = {Sayers, S and Anujan, P and Yu, H and Palmer, S and Nautiyal, J and Franks, S and Hanyaloglu, A},
doi = {10.3389/fendo.2021.798866},
journal = {Frontiers in Endocrinology},
pages = {1--15},
title = {Follicle-stimulating hormone induces lipid droplets via Gαi/o and β- arrestin in an endometrial cancer cell line},
url = {http://dx.doi.org/10.3389/fendo.2021.798866},
volume = {12},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Follicle-stimulating hormone (FSH) and its G protein-coupled receptor, FSHR, represents a paradigm for receptor signaling systems that activate multiple and complex pathways. Classically, FSHR activates Gαs to increase intracellular levels of cAMP, but its ability to activate other G proteins, and β-arrestin-mediated signaling is well documented in many different cell systems. The pleiotropic signal capacity of FSHR offers a mechanism for how FSH drives multiple and dynamic downstream functions in both gonadal and non-gonadal cell types, including distinct diseases, and how signal bias may be achieved at a pharmacological and cell system-specific manner. In this study, we identify an additional mechanism of FSH-mediated signaling and downstream function in the endometrial adenocarcinoma Ishikawa cell line. While FSH did not induce increases in cAMP levels, this hormone potently activated pertussis toxin sensitive Gαi/o signaling. A selective allosteric FSHR ligand, B3, also activated Gαi/o signaling in these cells, supporting a role for receptor-mediated activation despite the low levels of FSHR mRNA. The low expression levels may attribute to the lack of Gαs/cAMP signaling as increasing FSHR expression resulted in FSH-mediated activation of the Gαs pathway. Unlike prior reports for FSH-mediated Gαs/cAMP signaling, FSH-mediated Gαi/o signaling was not affected by inhibition of dynamin-dependent receptor internalization. While chronic FSH did not alter cell viability, FSH was able to increase lipid droplet size. The β-arrestins are key adaptor proteins known to regulate FSHR signaling. Indeed, a rapid, FSH-dependent increase in interactions between β-arrestin1 and Gαi1 was observed via NanoBiT complementation in Ishikawa cells. Furthermore, both inhibition of Gαi/o signaling and siRNA knockdown of β-arrestin 1/2 significantly reduced FSH-induced lipid droplet accumulation, implying a role for a
AU  - Sayers,S
AU  - Anujan,P
AU  - Yu,H
AU  - Palmer,S
AU  - Nautiyal,J
AU  - Franks,S
AU  - Hanyaloglu,A
DO  - 10.3389/fendo.2021.798866
EP  - 15
PY  - 2022///
SN  - 1664-2392
SP  - 1
TI  - Follicle-stimulating hormone induces lipid droplets via Gαi/o and β- arrestin in an endometrial cancer cell line
T2  - Frontiers in Endocrinology
UR  - http://dx.doi.org/10.3389/fendo.2021.798866
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2021.798866/full
UR  - http://hdl.handle.net/10044/1/93691
VL  - 12
ER  -
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