RT Journal Article SR Electronic T1 The Angiotensin II Type 1 Receptor Induces Membrane Blebbing by Coupling to Rho A, Rho Kinase, and Myosin Light Chain Kinase JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 903 OP 911 DO 10.1124/mol.110.063859 VO 77 IS 6 A1 Christina M. Godin A1 Stephen S. G. Ferguson YR 2010 UL http://molpharm.aspetjournals.org/content/77/6/903.abstract AB The angiotensin II type 1 receptor (AT1R) is a Gαq/11-coupled G protein-coupled receptor that is widely expressed in multiple tissues, including vascular smooth muscle cells, brain, and kidney. Activation of the AT1R in vascular smooth muscle cells leads to alterations in actin-based membrane protrusions such as lamellipodia, filopodia, and membrane blebs that ultimately lead to cell migration, which is important for the regulation of vascular tone. In the present study, we examine the role of small G proteins in mediating AT1R-induced alterations in membrane dynamics in human embryonic kidney 293 cells. We find that the activation of the AT1R with 100 nM angiotensin II results in the rapid formation of membrane blebs at early time points of agonist stimulation that cease within 40 min of agonist stimulation. AT1R-stimulated membrane bleb formation is independent of RalA, RalB, Rac1, cdc42, Arf6, and Ras, but it involves RhoA. Furthermore, membrane blebbing activated by the AT1R is attenuated in the presence of the β-arrestin amino-terminal domain, Ral GDP dissociation stimulator (RalGDS) β-arrestin binding domain, and short interfering RNA (siRNA) depletion of β-arrestin2. However, siRNA depletion of RalGDS protein did not affect membrane blebbing in response to AT1R activation. The inhibition of the downstream RhoA effectors Rho kinase (ROCK) and myosin light chain kinase (MLCK) effectively attenuated AT1R-mediated membrane blebbing. Thus, we show that membrane blebbing in response to AT1R signaling is dependent on β-arrestin2 and is mediated by a RhoA/ROCK/MLCK-dependent pathway. Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics