Table 1.
β-arrestin and arrestin-domain containing protein interactions that function in GPCR trafficking
| Binding Partner | Functional Role | References |
|---|---|---|
| β-arrestins | ||
| β2-adaptin | Directly interacts with β-arrestins and facilitates GPCR endocytosis | Laporte et al. 2001 Edeling et al. 2006 Schmid et al. 2006 |
| μ2-adaptin | Preferentially interacts with β-arrestin2 and facilitates endocytosis of the β2AR | Marion et al. 2007 |
| Clathrin | Directly interacts with β-arrestins and facilitates GPCR endocytosis |
Goodman et al. 1996 ter Haar et al. 2000 Kang et al. 2009 |
| PIP2 | Directly interacts with β-arrestins and enhances GPCR endocytosis |
Gaidarov et al. 1999 Nelson et al. 2008 |
| PIP5K-Iα | Directly interacts with β-arrestin2 and facilitates β2AR endocytosis | Nelson et al. 2008 |
| IP6 | Directly interacts with β-arrestins; inhibits β-arrestin/GPCR interaction; facilitates β- arrestin oligomerization; regulates β-arrestin cellular localization |
Gaidarov et al. 1999 Storez et al. 2005 Milano et al. 2006 |
| PI3K | Regulates β2AR endocytosis by AP2 recruitment to the β2AR/β-arrestin complex | Naga Prasad et al. 2002 |
| NSF | Directly interacts with β-arrestin2 and enhances endocytosis of the β2AR | McDonald et al. 1999 |
| ARF6 | GDP-bound form interacts with β-arrestin1 and enhances GPCR endocytosis and degradation and negatively controls recycling |
Claing et al. 2001 Houndolo et al. 2005 Macia et al. 2012 |
| ARNO | Activates ARF6 and facilitates β-arrestin release from the luteinizing hormone/choriogonadotropin receptor | Mukherjee et al. 2000 |
| EFA6 | β-arrestin1 binds ARF6-GDP and EFA6 and facilitates ARF6 activation leading to β2AR degradation | Macia et al. 2012 |
| AGAP2 | AGAP2 interacts with β-arrestin1 and 2 and facilitates β-arrestin association with the β2AR and regulates β2AR recycling | Wu et al., 2013 |
| Mdm2 | Ubiquitinates β-arrestin2 and facilitates the endocytosis of β2AR |
Shenoy et al. 2001 Song et al, 2007 |
| parkin | Directly interacts with β-arrestin and facilitates Mdm2 interaction | Ahmed at al., 2011 |
| AIP4 | Interacts with β-arrestin2 on early endosomes and facilitates CXCR4 degradation | Bhandari et al. 2007 |
| Nedd4 | Interacts with β-arrestin to facilitate β2AR ubiquitination and trafficking |
Shenoy et al. 2008 Han et al. 2013 |
| Smurf2 | Interacts with β-arrestin2 and mediates μ-opioid receptor ubiquitination and trafficking | Henry et al., 2012 |
| USP20 | Directly deubiquitinates β-arrestin2 and β2AR to prevent receptor degradation | Shenoy et al. 2009 |
| USP33 | Directly deubiquitinates β-arrestin2 and β2AR to prevent receptor degradation | Berthouze et al. 2009 |
| STAM-1 | Interacts with β-arrestin1 to regulate CXCR4 sorting | Malik & Marchese 2010 |
| eNOS | Interacts with and s-nitrosylates β-arrestin2 and facilitates β-arrestin2 binding with clathrin and β-adaptin; promotes receptor internalization | Ozawa et al. 2008 |
| NHERF | Interacts with β-arrestin1 to regulate P2Y12 receptor internalization | Nisar et al. 2012 |
| Arrestin-domain containing proteins (ARRDCs) | ||
| Nedd4 | Directly interacts with the PPXY motifs of ARRDC3 to promote β2AR ubiquitination and degradation ARRDC3 interacts with Nedd4-β2AR upon agonist stimulation to recruit the complex to endosomes |
Nabhan et al. 2010 Han et al. 2013 |
| β-arrestins | Form heterodimers with ARRDC1 to mediate Notch ubiquitination and degradation | Puca et al. 2013 |
| Itch/AIP4 | Interacts with ARRDC3 Interacts with ARRDC2, ARRDC3 and TXNIP Interacts with ARRDC1 to mediate Notch ubiquitination and degradatio |
Nabhan et al. 2010 Rauch et al. 2011 Puca et al. 2013 |
| ALIX | Interacts with ARRDC1, 2 and 3 via its proline-rich domain (PRR) | Rauch et al. 2011 |
| HRS | Interacts with the PPXY motifs of ARRDC3 |
Han et al. 2013 Shea et al. 2013 |
| Clathrin | Interacts with ARRDC3/4 under basal conditions, interaction decreases upon agonist stimulation | Shea et al. 2013 |
| WWP1 | Interacts with all five ARRDCs |
Nabhan et al. 2010 Rauch et al. 2011 |
| WWP2 | Interacts with all ARRDCs except ARRDC4 |
Nabhan et al. 2010 Rauch et al. 2011 |