Arrestins are elongated molecules, in which several intra-molecular interactions hold the relative orientation of the two domains.
In unstimulated cell arrestins are localized in the cytoplasm in this basal “inactive” conformation.
Active phosphorylated GPCRs recruit arrestin to the plasma membrane.
Receptor binding induces a global conformational change that involves the movement of the two arrestin domains and the release of its C-terminal tail that contains clathrin and AP2 binding sites.
Increased accessibility of these sites in receptor-bound arrestin targets the arrestin-receptor complex to the coated pit.
Arrestins also bind microtubules (part of the cellular “skeleton”), where they assume yet another conformation, different from both free and receptor-bound form.
Microtubule-bound arrestins recruit certain proteins to the cytoskeleton, which affects their activity and/or redirects it to microtubule-associated proteins.

Arrestins shuttle between cell nucleus and cytoplasm.
Their nuclear functions are not fully understood, but it was shown that all four mammalian arrestin subtypes remove some of their partners, such as protein kinase JNK3 or the ubiquitin ligase Mdm2, from the nucleus.
Arrestins also modify gene expression by enhancing transcription of certain genes.
Arrestins are elongated molecules, in which several intra-molecular interactions hold the relative orientation of the two domains. In unstimulated cell arrestins are localized in the cytoplasm in this basal “inactive” conformation. Active phosphorylated GPCRs recruit arrestin to the plasma membrane. Receptor binding induces a global conformational change that involves the movement of the two arrestin domains and the release of its C-terminal tail that contains clathrin and AP2 binding sites. Increased accessibility of these sites in receptor-bound arrestin targets the arrestin-receptor complex to the coated pit. Arrestins also bind microtubules (part of the cellular “skeleton”), where they assume yet another conformation, different from both free and receptor-bound form. Microtubule-bound arrestins recruit certain proteins to the cytoskeleton, which affects their activity and/or redirects it to microtubule-associated proteins.
Arrestins shuttle between cell nucleus and cytoplasm. Their nuclear functions are not fully understood, but it was shown that all four mammalian arrestin subtypes remove some of their partners, such as protein kinase JNK3 or the ubiquitin ligase Mdm2, from the nucleus. Arrestins also modify gene expression by enhancing transcription of certain genes.
Arrestin