Imperial College London
Portrait Picture

ProfessorAylinHanyaloglu

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor in Molecular Medicine
 
 
 
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Contact

 

+44 (0)20 7594 2128a.hanyaloglu Website

 
 
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Assistant

 

Miss Kiran Dosanjh +44 (0)20 7594 2176

 
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Location

 

2009Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jonas:2018:10.1038/s41598-018-20722-5,
author = {Jonas, KC and Chen, S and Virta, M and Mora, J and Franks, S and Huhtaniemi, I and Hanyaloglu, AC},
doi = {10.1038/s41598-018-20722-5},
journal = {Scientific Reports},
title = {Temporal reprogramming of calcium signalling via crosstalk of gonadotrophin receptors that associate as functionally asymmetric heteromers},
url = {http://dx.doi.org/10.1038/s41598-018-20722-5},
volume = {8},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Signal crosstalk between distinct G protein-coupled receptors (GPCRs) is one mechanism that underlies pleiotropic signalling. Such crosstalk is also pertinent for GPCRs activated by gonadotrophic hormones; follicle-stimulating hormone (FSH) and luteinising hormone (LH), with specific relevance to female reproduction. Here, we demonstrate that gonadotrophin receptor crosstalk alters LH-induced Gαq/11-calcium profiles. LH-induced calcium signals in both heterologous and primary human granulosa cells were prolonged by FSHR coexpression via influx of extracellular calcium in a receptor specific manner. LHR/FSHR crosstalk involves Gαq/11 activation as a Gαq/11 inhibitor abolished calcium responses. Interestingly, the enhanced LH-mediated calcium signalling induced by FSHR co-expression was dependent on intracellular calcium store release and involved Gβγ. Biophysical analysis of receptor and Gαq interactions indicated that ligand-dependent association between LHR and Gαq was rearranged in the presence of FSHR, enabling FSHR to closely associate with Gαq following LHR activation. This suggests that crosstalk may occur via close associations as heteromers. Super-resolution imaging revealed that LHR and FSHR formed constitutive heteromers at the plasma membrane. Intriguingly, the ratio of LHR:FSHR in heterotetramers was specifically altered following LH treatment. We propose that functionally significant FSHR/LHR crosstalk reprograms LH-mediated calcium signalling at the interface of receptor-G protein via formation of asymmetric complexes.
AU  - Jonas,KC
AU  - Chen,S
AU  - Virta,M
AU  - Mora,J
AU  - Franks,S
AU  - Huhtaniemi,I
AU  - Hanyaloglu,AC
DO  - 10.1038/s41598-018-20722-5
PY  - 2018///
SN  - 2045-2322
TI  - Temporal reprogramming of calcium signalling via crosstalk of gonadotrophin receptors that associate as functionally asymmetric heteromers
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-018-20722-5
UR  - http://hdl.handle.net/10044/1/56285
VL  - 8
ER  -
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