DOPr oligomerization: functional and pharmacological consequences
| Oligomer Name | Detection Technique | Detection In Vivo | Binding Properties | G Protein Coupling and Signaling | Internalization and Trafficking | Reference |
|---|---|---|---|---|---|---|
| DOPr-DOPr | Denaturating SDS-PAGE, coimmunoprecipitation, BRET | Not reported | Not changed | Not changed | Not changed | Simonds et al. (1985), Cvejic and Devi (1997), McVey et al. (2001), Ramsay et al. (2002), Sarkar et al., 2012 |
| DOPr-KOPr | Coimmunoprecipitation, BRET | Not reported | Decreased binding affinity for DOPr or KOPr, cooperativity when DOPr and KOPr ligands are administered together | Potentiation of cAMP inhibition and the ERK1/2 activation | Decreased etorphine-induced internalization | Jordan and Devi (1999), Ramsay et al. (2002), Berg et al. (2012) |
| DOPr-MOPr | Coimmunoprecipitation, BRET, immunolocalization with a DOPr-MOPr heteromer-specific antibody, TAT peptide disruption | Coimmunoprecipitation, immunolocalization with a DOPr-MOPr heteromer-specific antibody | Decreased affinity for synthetic ligands, increased affinity for endogenous opioid peptides, allosteric modulation of DOPr and MOPr ligand binding | Shifts from Gαi to Gaz coupling, turns MOPr functions from inhibitory to excitatory, potentiation of cAMP inhibition and the ERK1/2 activation, shifts ERK1/2 activation from transient to sustained | Ligand-specific cointernalization of DOPr or MOPr | George et al. (2000), Gomes et al. (2000, 2004, 2011), Charles et al. (2003), Fan et al. (2005), Law et al. (2005), Rozenfeld and Devi (2007), Xie et al. (2009), Gupta et al. (2010); Kabli et al. (2010), He et al. (2011), Milan-Lobo and Whistler (2011), Sarkar et al. (2012), Erbs et al. (2015) |
| DOPr-β2AR | Coimmunoprecipitation, BRET, FRET | Not reported | Not changed | Not changed | Nonstimulated DOPr cointernalizes with β2AR | Jordan et al. (2001), McVey et al. (2001), Ramsay et al. (2002), Cao et al. (2005) |
| DOPr-α2AAR | Coimmunoprecipitation, FRET | Not reported | Not reported | α2AAR potentiates DOPr-mediated neurites outgrowth | Not reported | Rios et al. (2004) |
| DOPr-α1AAR | BRET | Not reported | Not reported | Not reported | Not reported | Ramsay et al. (2004) |
| DOPr-CCR5 | Coimmunoprecipitation, crosslinking agents | Not reported | Not reported | Not reported | Not reported | Suzuki et al. (2002) |
| DOPr-CXCR4 | Coimmunoprecipitation, FRET | Not reported | Not changed | The DOPr-CXCR4 hetero-oligomer cannot be activated by agonists | Not changed | Pello et al. (2008) |
| DOPr-CXCR2 | Coimmunoprecipitation, BRET, FRET | Not reported | Not changed | CXCR2 antagonist increased DOPr- mediated G protein activation | Not reported | Parenty et al. (2008) |
| DOPr-SNSR-4 | BRET | Not reported | Not changed | SNSR-4 activation reduced DOPr- mediated signaling | Not reported | Breit et al. (2006) |
| DOPr-SSTR4 | Coimmunoprecipitation, FRET | Coimmunoprecipitation, FRET | Not reported | Synergistic effect on receptor- mediated sgnaling | Activation of both receptors retained them at the cell surface | Somvanshi and Kumar (2014) |
| DOPr-CB1 | Coimmunoprecipitation, BRET | Immunolocalization with a DOPr-, CB1 heteromer-specific antibody | Increased binding of DOPr ligands upon CB1 occupancy | Decreased CB1-mediated signaling, increased DOPr-mediated signaling | Altered CB1 localization | Bushlin et al. (2012), Rozenfeld et al. (2012) |
SNSR-4, sensory neuron–specific receptor subtype 4; SSTR, somatostatin type 4 receptor.