Imperial College London
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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{Jean-Alphonse:2014:10.1074/jbc.M113.526350,
author = {Jean-Alphonse, F and Bowersox, S and Chen, S and Beard, G and Puthenveedu, MA and Hanyaloglu, AC},
doi = {10.1074/jbc.M113.526350},
journal = {Journal of Biological Chemistry},
pages = {3960--3977},
title = {Spatially restricted G protein-coupled receptor signaling via divergent endocytic compartments},
url = {http://dx.doi.org/10.1074/jbc.M113.526350},
volume = {289},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Postendocytic sorting of G protein-coupled receptors (GPCRs) is driven by their interactions between highly diverse receptor sequence motifs with their interacting proteins, such as postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), zonula occludens-1 protein (zo-1) (PDZ) domain proteins. However, whether these diverse interactions provide an underlying functional specificity, in addition to driving sorting, is unknown. Here we identify GPCRs that recycle via distinct PDZ ligand/PDZ protein pairs that exploit their recycling machinery primarily for targeted endosomal localization and signaling specificity. The luteinizing hormone receptor (LHR) and β2-adrenergic receptor (B2AR), two GPCRs sorted to the regulated recycling pathway, underwent divergent trafficking to distinct endosomal compartments. Unlike B2AR, which traffics to early endosomes (EE), LHR internalizes to distinct pre-early endosomes (pre-EEs) for its recycling. Pre-EE localization required interactions of the LHR C-terminal tail with the PDZ protein GAIP-interacting protein C terminus, inhibiting its traffic to EEs. Rerouting the LHR to EEs, or EE-localized GPCRs to pre-EEs, spatially reprograms MAPK signaling. Furthermore, LHR-mediated activation of MAPK signaling requires internalization and is maintained upon loss of the EE compartment. We propose that combinatorial specificity between GPCR sorting sequences and interacting proteins dictates an unprecedented spatiotemporal control in GPCR signal activity.
AU  - Jean-Alphonse,F
AU  - Bowersox,S
AU  - Chen,S
AU  - Beard,G
AU  - Puthenveedu,MA
AU  - Hanyaloglu,AC
DO  - 10.1074/jbc.M113.526350
EP  - 3977
PY  - 2014///
SN  - 1083-351X
SP  - 3960
TI  - Spatially restricted G protein-coupled receptor signaling via divergent endocytic compartments
T2  - Journal of Biological Chemistry
UR  - http://dx.doi.org/10.1074/jbc.M113.526350
UR  - https://www.sciencedirect.com/science/article/pii/S0021925820441833?via%3Dihub
UR  - http://hdl.handle.net/10044/1/31196
VL  - 289
ER  -
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