PT  - JOURNAL ARTICLE
AU  - Jungah Min
AU  - Kathryn A DeFea
TI  - β-arrestin-dependent Actin Reorganization: Bringing the Right Players Together at the Leading Edge
AID  - 10.1124/mol.111.072470
DP  - 2011 Aug 11
TA  - Molecular Pharmacology
PG  - mol.111.072470
4099  - http://molpharm.aspetjournals.org/content/early/2011/08/11/mol.111.072470.short
4100  - http://molpharm.aspetjournals.org/content/early/2011/08/11/mol.111.072470.full
AB  - First identified as mediators of G-protein-coupled receptor desensitization and internalization and later as signaling platforms, β-arrestins play a requisite role in chemotaxis and reorganization of the actin cytoskeleton, downstream of multiple receptors. However, the precise molecular mechanisms underlying their involvement have remained elusive. Initial interest in β-arrestins as facilitators of cell migration and actin reorganization stemmed from the known interplay between receptor endocytosis and actin filament formation-as disruption of the actin cytoskeleton inhibits these β-arrestin-dependent events. With growing interest in the mechanisms by which cells can sense a gradient of agonist during cell migration, investigators began to hypothesize that β-arrestins may contribute to directed migration by controlling chemotactic receptor turnover at the plasma membrane. Finally, increasing evidence emerged that β-arrestins are more than just clathrin adaptor proteins involved in turning off receptor signals, but are actually capable of generating their own signals by scaffolding signaling molecules and controlling the activity of multiple cellular enzymes. This new role of β-arrestins as signaling scaffolds has led to the hypothesis that they can facilitate cell migration by sequestering actin assembly activities and upstream regulators of actin assembly at the leading edge. This review discusses recent advances in our understanding of how β-arrestin scaffolds contribute to cell migration, focusing on recently identified β-arrestin interacting proteins and phosphorylation targets that have known roles in actin reorganization.