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In a recent work, the group of von Zastrow showed that after being recruited by the phosphorylated MOR, arrestin 3 acts as a scaffold, promoting ubiquitination of two lysyl residues in the first intracellular loop by the ubiquitin ligase Smurf2 (Henry et al., DPDPE also enables arrestin-mediated endocytosis of DOR as shown by the partial reduction of internalization when arrestins 2 or 3 are selectively inhibited (Zhang et al., 2005)

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Taken together, these heterogeneous findings highlight both biological plausibility and the methodological constraints that shape the current evidence base, motivating the integrative Discussion below

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