Cannabinoid receptor 2 undergoes Rab5-mediated internalization and recycles via a Rab11-dependent pathway
| Autor: | Natasha L. Grimsey, Catherine E. Goodfellow, Michelle Glass, Mike Dragunow |
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| Rok vydání: | 2011 |
| Předmět: |
Agonist
Endosome medicine.drug_class media_common.quotation_subject education Protein trafficking Biological Transport Active Biology Receptor Cannabinoid CB2 Rab GTP-binding protein Cannabinoid receptor type 2 medicine Humans Inverse agonist Internalization Receptor Molecular Biology rab5 GTP-Binding Proteins G protein-coupled receptor media_common Cell Membrane Cannabinoid receptor CB2 Cell Biology Endocytosis Cell biology Kinetics HEK293 Cells rab GTP-Binding Proteins Cell Surface receptor lipids (amino acids peptides and proteins) Signal transduction Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1813(8):1554-1560 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2011.05.010 |
| Popis: | Cannabinoid receptor 2 (CB2) is a GPCR highly expressed on the surface of cells of the immune system, supporting its role in immunomodulation. This study has investigated the trafficking properties of this receptor when stably expressed by HEK-293 cells. As previously reported, cell surface CB2 rapidly internalized upon exposure to agonist. Direct evidence of CB2 recycling was observed upon competitive removal of the stimulating agonist by inverse agonist. CB2 also underwent slow constitutive internalization when agonist was absent and was up-regulated in the presence of inverse agonist. Co-expression of CB2 and dominant negative Rab5 resulted in a significantly reduced capacity for receptors to internalize with no effect on recycling of the internalized receptors. Conversely, co-expression with dominant negative Rab11 did not alter the ability of CB2 to internalize but did impair their ability to return to the cell surface. Co-expression of wild-type, dominant negative or constitutively active Rab4 with CB2 did not alter basal surface expression, extent of internalization, or extent of recycling. These results suggest that Rab5 is involved in CB2 endocytosis and that internalized receptors are recycled via a Rab11 associated pathway rather than the rapid Rab4 associated pathway. This report provides the first comprehensive description of CB2 internalization and recycling to date. |
| Databáze: | OpenAIRE |
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