β-Arrestin multimers: does a crowd help or hinder function?

In this issue of the Biochemical Journal, Xu et al. describe how they use a spot peptide array to identify a unique sequence within beta-arrestin-2 that is required for both multimerization and ERK1/2 (extracellular-signal-related kinase 1/2) scaffolding. They provide evidence that dimers may serve as more than just 'storage forms' of beta-arrestins, incapable of interacting with receptors but, rather, perhaps, adding to the specificity of G-protein-coupled-receptor signalling. They show that key charged residues within this dimerization interface of beta-arrestin-2 block association with ERK1/2 and subsequent activation of ERK1/2 by beta(2)-adrenergic receptors, while internalization is unaffected. They suggest that self-association may serve as a means of sheltering scaffolding sites on beta-arrestins from specific binding partners to prevent constitutive activation of key signalling pathways. These studies enhance our understanding of how beta-arrestins can juggle their roles as scaffolds of multiple pathways in response to diverse signals.