Receptor heteromerization expands the repertoire of cannabinoid signaling in rodent neurons
| العنوان: | Receptor heteromerization expands the repertoire of cannabinoid signaling in rodent neurons |
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| المؤلفون: | Ittai Bushlin, Ivone Gomes, Lakshmi A. Devi, Alexander Lachmann, Achla Gupta, Avi Ma'ayan, Raphael Rozenfeld, G. Luca Gusella, Lorenzo Battini, Susana R. Neves, Robert D. Blitzer, Nikos Tzavaras |
| المصدر: | PLoS ONE PLoS ONE, Vol 7, Iss 1, p e29239 (2012) |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Cannabinoid receptor, Arrestins, medicine.medical_treatment, lcsh:Medicine, Apoptosis, Biochemistry, Mice, 0302 clinical medicine, Receptor, Cannabinoid, CB1, Receptors, Opioid, delta, lcsh:Science, Receptor, Extracellular Signal-Regulated MAP Kinases, Cerebral Cortex, Neurons, 0303 health sciences, Multidisciplinary, Neurochemistry, Endocannabinoid system, Cell biology, Protein Transport, Signal transduction, Neurochemicals, Signal Transduction, Research Article, G protein, Cell Survival, Biology, Cell Line, δ-opioid receptor, 03 medical and health sciences, medicine, Animals, Humans, Protein Structure, Quaternary, Protein Interactions, 030304 developmental biology, G protein-coupled receptor, Cell Proliferation, Cannabinoids, lcsh:R, Proteins, Regulatory Proteins, Transmembrane Proteins, Gene Expression Regulation, Cellular Neuroscience, lcsh:Q, Cannabinoid, Protein Multimerization, 030217 neurology & neurosurgery, Neuroscience, Endocannabinoids |
| الوصف: | 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. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14a0b8e55fe8b2e295a6002a22f9a59e https://pubmed.ncbi.nlm.nih.gov/22235275 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....14a0b8e55fe8b2e295a6002a22f9a59e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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