Regulation of cell adhesion and motility: a novel function of arrestin proteins

Abstract

Arrestins bind G protein‐coupled receptors and more than 100 non‐receptor partners, regulating various signaling pathways and cellular functions. The interactions of many proteins (e.g., Src, JNK3, ERK½, Mdm2, etc.) with receptor‐bound arrestin localize these molecules to receptor‐rich membranes. Our recent finding that arrestins bind microtubules and recruit signaling proteins to the cytoskeleton prompted us to investigate whether arrestins affect cell adhesion, motility, and morphology. Here we show that arrestin double knock‐out (DKO) and arrestin2 knock‐out (A2 KO) cells stained with Rhodamine‐Phalloidin look drastically different than arrestin3 knock‐out (A3 KO) and wild type (WT) cells. DKO cells appear to spread in an integrin‐independent manner, in contrast to its single knock‐out and WT counterparts. Additionally, DKO cells show a significant deficit in cell adhesion to extracellular matrix protein fibronectin, whereas A2 KO cells show a dramatic increase. WT and A3 KO cells are similar. DKO cells have dramatically decreased active Rho compared to A3 KO and WT cells. Thus, arrestins differentially regulate cell adhesion and spreading.NIH Grants GM77561, GM081756 (VVG), VA Merit Award (RZ), training grant EY07135 (WMC).