Resistance of the dopamine D4 receptor to agonist-induced internalization and degradation

The Chemokine Receptor CCR1 Is Constitutively Active, Which Leads to G Protein-independent, β-Arrestin-mediated Internalization

“…For example, a constitutively active mutant of CXCR4 was shown to be basally phosphorylated and internalized (43,82), whereas the D6 decoy chemokine receptor is constitutively internalized in a phosphorylation-independent manner (83). Additionally, the dopamine D4 receptor is constitutively phosphorylated but not internalized (84). Therefore, whether or not the constitutively active CCR1 was continually internalized was addressed first, followed by whether basal phosphorylation was evident.…”

Repeated application of Modafinil and Levodopa reveals a drug-independent precise timing of spatial working memory modulation

“…Similarily, D2 receptors show agonist-dependent internalization [26]. In contrast, D4 receptors are resistant to agonist induced receptor internalization and degradation as tested in human cell lines [27]. D3 receptor tolerance by repeated agonist stimulation is realized by changes in receptor confirmation rather than desensitization or internalization [28].…”

Dopamine receptor D4 internalization requires a beta-arrestin and a visual arrestin

“…The previous work on DRD4 desensitization has investigated the role of the β-arrestins because of their ubiquitous expression and interaction with many different GPCRs (Spooren et al, 2010;Cho et al, 2010). However, there are two other arrestin proteins expressed in mammalian tissues.…”

“…The desensitization of the D2-like receptors has been studied, and DRD2 and DRD3 are internalized after dopamine stimulation, as long as a β-arrestin is present (Kim et al, 2001;Namkung and Sibley, 2004). The most recent research on DRD4 showed that it is able to bind β-arrestin, but it is not internalized (Spooren et al, 2010).…”

“…with DRD4, which occurs with or without DA stimulation (Spooren et al, 2010). Co-IP with ARR1 was also tested with the appropriate controls and an ARR1-specific A C C E P T E D M A N U S C R I P T…”