Title |
Receptor Heteromerization Expands the Repertoire of Cannabinoid Signaling in Rodent Neurons
|
---|---|
Published in |
PLOS ONE, January 2012
|
DOI | 10.1371/journal.pone.0029239 |
Pubmed ID | |
Authors |
Raphael Rozenfeld, Ittai Bushlin, Ivone Gomes, Nikos Tzavaras, Achla Gupta, Susana Neves, Lorenzo Battini, G. Luca Gusella, Alexander Lachmann, Avi Ma'ayan, Robert D. Blitzer, Lakshmi A. Devi |
Abstract |
A fundamental question in G protein coupled receptor biology is how a single ligand acting at a specific receptor is able to induce a range of signaling that results in a variety of physiological responses. We focused on Type 1 cannabinoid receptor (CB₁R) as a model GPCR involved in a variety of processes spanning from analgesia and euphoria to neuronal development, survival and differentiation. We examined receptor dimerization as a possible mechanism underlying expanded signaling responses by a single ligand and focused on interactions between CB₁R and delta opioid receptor (DOR). Using co-immunoprecipitation assays as well as analysis of changes in receptor subcellular localization upon co-expression, we show that CB₁R and DOR form receptor heteromers. We find that heteromerization affects receptor signaling since the potency of the CB₁R ligand to stimulate G-protein activity is increased in the absence of DOR, suggesting that the decrease in CB₁R activity in the presence of DOR could, at least in part, be due to heteromerization. We also find that the decrease in activity is associated with enhanced PLC-dependent recruitment of arrestin3 to the CB₁R-DOR complex, suggesting that interaction with DOR enhances arrestin-mediated CB₁R desensitization. Additionally, presence of DOR facilitates signaling via a new CB₁R-mediated anti-apoptotic pathway leading to enhanced neuronal survival. Taken together, these results support a role for CB₁R-DOR heteromerization in diversification of endocannabinoid signaling and highlight the importance of heteromer-directed signal trafficking in enhancing the repertoire of GPCR signaling. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
United States | 1 | <1% |
Germany | 1 | <1% |
Unknown | 116 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 24 | 20% |
Researcher | 17 | 14% |
Student > Master | 15 | 13% |
Student > Bachelor | 13 | 11% |
Student > Doctoral Student | 11 | 9% |
Other | 21 | 18% |
Unknown | 18 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 31 | 26% |
Medicine and Dentistry | 17 | 14% |
Biochemistry, Genetics and Molecular Biology | 15 | 13% |
Neuroscience | 14 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 10 | 8% |
Other | 13 | 11% |
Unknown | 19 | 16% |