Abstract
Somatostatin regulates multiple biological functions by acting through a family of five G protein-coupled receptors, somatostatin receptors (SSTRs) 1-5. Although all five receptor subtypes inhibit adenylate cyclase activity and decrease intracellular cAMP levels, specific receptor subtypes also couple to additional signaling pathways. In CCL39 fibroblasts expressing either human SSTR1 or SSTR2, we demonstrate that activation of SSTR1 (but not SSTR2) attenuated both thrombin- and integrin-stimulated Rho-GTP complex formation. The reduction in Rho-GTP formation in the presence of somatostatin was associated with decreased translocation of Rho and LIM kinase to the plasma membrane and fewer focal contacts. Activation of Rho resulted in the formation of intracellular actin stress fibers and cell migration. In CCL39-R1 cells, somatostatin treatment prevented actin stress fiber assembly and attenuated thrombin-stimulated cell migration through Transwell membranes to basal levels. To show that native SSTR1 shares the ability to inhibit Rho activation, we demonstrated that somatostatin treatment of human umbilical vein endothelial cells attenuated thrombin-stimulated Rho-GTP accumulation. These data show for the first time that a G protein-coupled receptor, SSTR1, inhibits the activation of Rho, the assembly of focal adhesions and actin stress fibers, and cell migration.
Highlights
The low molecular mass GTPase Rho plays a central role in regulating organization of the actin-based cytoskeleton in mammalian cells
We report that somatostatin (SST), acting at the G protein-coupled receptors (GPCRs) subtype SSTR1, inhibits Rho activity, attenuates the assembly of actin stress fibers and focal adhesions, and inhibits cell migration
SSTR1 Inhibits Actin Stress Fiber Assembly and Rho Activation by Thrombin—Our initial studies investigated whether SST regulates stress fiber assembly in CCL39 fibroblasts stably expressing human SSTR1 or SSTR2
Summary
The low molecular mass GTPase Rho plays a central role in regulating organization of the actin-based cytoskeleton in mammalian cells. These data show for the first time that a G protein-coupled receptor, SSTR1, inhibits the activation of Rho, the assembly of focal adhesions and actin stress fibers, and cell migration.
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