Arrestin mobilizes signaling proteins to the cytoskeleton and redirects their activity.
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.
Hanson
Susan M
SM
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Cleghorn
Whitney M
WM
Francis
Derek J
DJ
Vishnivetskiy
Sergey A
SA
Raman
Dayanidhi
D
Song
Xiufeng
X
Nair
K Saidas
KS
Slepak
Vladlen Z
VZ
Klug
Candice S
CS
Gurevich
Vsevolod V
VV
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
D019393:Arrestin; D014404:Tubulin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D048049:Extracellular Signal-Regulated MAP Kinases