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Actin cytoskeleton-dependent regulation of corticotropin-releasing factor receptor heteromers
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Hasdemir, Burcu, Mahajan, Shilpi, Oses-Prieto, Juan, Chand, Shreya, Woolley, Michael J., Burlingame, Alma, Grammatopoulos, Dimitris K. and Bhargava, Aditi (2017) Actin cytoskeleton-dependent regulation of corticotropin-releasing factor receptor heteromers. Molecular Biology of the Cell, 28 (18). pp. 2386-2399. doi:10.1091/mbc.e16-11-0778
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WRAP-actin-cytoskeleton-dependent-corticotropin-receptor-Woolley-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial Share Alike. Download (3299Kb) | Preview |
Official URL: https://doi.org/10.1091/mbc.e16-11-0778
Abstract
Stress responses are highly nuanced and variable, but how this diversity is achieved by modulating receptor function is largely unknown. Corticotropin-releasing factor receptors (CRFRs), class B G protein–coupled receptors, are pivotal in mediating stress responses. Here we show that the two known CRFRs interact to form heteromeric complexes in HEK293 cells coexpressing both CRFRs and in vivo in mouse pancreas. Coimmunoprecipitation and mass spectrometry confirmed the presence of both CRF1R and CRF2βR, along with actin in these heteromeric complexes. Inhibition of actin filament polymerization prevented the transport of CRF2βR to the cell surface but had no effect on CRF1R. Transport of CRF1R when coexpressed with CRF2βR became actin dependent. Simultaneous stimulation of cells coexpressing CRF1R+CRF2βR with their respective high-affinity agonists, CRF+urocortin2, resulted in approximately twofold increases in peak Ca2+responses, whereas stimulation with urocortin1 that binds both receptors with 10-fold higher affinity did not. The ability of CRFRs to form heteromeric complexes in association with regulatory proteins is one mechanism to achieve diverse and nuanced function.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||||
| Journal or Publication Title: | Molecular Biology of the Cell | ||||||||
| Publisher: | American Society for Cell Biology (ASCB) | ||||||||
| ISSN: | 1939-4586 | ||||||||
| Official Date: | 1 September 2017 | ||||||||
| Dates: |
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| Volume: | 28 | ||||||||
| Number: | 18 | ||||||||
| Page Range: | pp. 2386-2399 | ||||||||
| DOI: | 10.1091/mbc.e16-11-0778 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access |
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