title: Arrestin mobilizes signaling proteins to the cytoskeleton and redirects their activity.
abstract: Arrestins regulate the activity and subcellular localization of G protein-coupled receptors and other signaling molecules. Here, we demonstrate that arrestins bind microtubules (MTs) in vitro and in vivo. The MT-binding site on arrestins overlaps significantly with the receptor-binding site, but the conformations of MT-bound and receptor-bound arrestin are different. Arrestins recruit ERK1/2 and the E3 ubiquitin ligase Mdm2 to MTs in cells, similar to the arrestin-dependent mobilization of these proteins to the receptor. Arrestin-mediated sequestration of ERK to MTs reduces the level of ERK activation. In contrast, recruitment of Mdm2 to MTs by arrestin channels Mdm2 activity toward cytoskeleton-associated proteins, increasing their ubiquitination dramatically. The mobilization of signaling molecules to MTs is a novel biological function of arrestin proteins.
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hanson
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Cleghorn
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Francis
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Vishnivetskiy
authors.forename: Dayanidhi
authors.initials: D
authors.lastname: Raman
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Song
authors.forename: K Saidas
authors.initials: KS
authors.lastname: Nair
authors.forename: Vladlen Z
authors.initials: VZ
authors.lastname: Slepak
authors.forename: Candice S
authors.initials: CS
authors.lastname: Klug
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Gurevich
mesh_terms: D000818:Animals; D019393:Arrestin / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival; D002522:Chlorocebus aethiops; D019281:Dimerization; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D021381:Protein Transport; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism
chemical_list: D019393:Arrestin; D014404:Tubulin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D048049:Extracellular Signal-Regulated MAP Kinases