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{Gorvin:2018:10.1016/j.celrep.2017.12.089,
author = {Gorvin, CM and Rogers, A and Hastoy, B and Tarasov, AI and Frost, M and Sposini, S and Inoue, A and Whyte, MP and Rorsman, P and Hanyaloglu, AC and Breitwieser, GE and Thakker, RV},
doi = {10.1016/j.celrep.2017.12.089},
journal = {Cell Reports},
pages = {1054--1066},
title = {AP2? Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity.},
url = {http://dx.doi.org/10.1016/j.celrep.2017.12.089},
volume = {22},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Spatial control of G-protein-coupled receptor (GPCR) signaling, which is used by cells to translate complex information into distinct downstream responses, is achieved by using plasma membrane (PM) and endocytic-derived signaling pathways. The roles of the endomembrane in regulating such pleiotropic signaling via multiple G-protein pathways remain unknown. Here, we investigated the effects of disease-causing mutations of the adaptor protein-2 ? subunit (AP2?) on signaling by the class C GPCR calcium-sensing receptor (CaSR). These AP2? mutations increase CaSR PM expression yet paradoxically reduce CaSR signaling. Hypercalcemia-associated AP2? mutations reduced CaSR signaling via G?q/11 and G?i/o pathways. The mutations also delayed CaSR internalization due to prolonged residency time of CaSR in clathrin structures that impaired or abolished endosomal signaling, which was predominantly mediated by G?q/11. Thus, compartmental bias for CaSR-mediated G?q/11 endomembrane signaling provides a mechanistic basis for multidimensional GPCR signaling.
AU  - Gorvin,CM
AU  - Rogers,A
AU  - Hastoy,B
AU  - Tarasov,AI
AU  - Frost,M
AU  - Sposini,S
AU  - Inoue,A
AU  - Whyte,MP
AU  - Rorsman,P
AU  - Hanyaloglu,AC
AU  - Breitwieser,GE
AU  - Thakker,RV
DO  - 10.1016/j.celrep.2017.12.089
EP  - 1066
PY  - 2018///
SN  - 2211-1247
SP  - 1054
TI  - AP2? Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity.
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2017.12.089
UR  - http://hdl.handle.net/10044/1/57074
VL  - 22
ER  -
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