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Rac Activation (rac + activation)
Selected AbstractsPhospholipase,C, negatively regulates Rac/Cdc42 activation in antigen-stimulated mast cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Mirvat El-Sibai M.D. Abstract The Rho GTPases Rac and Cdc42 play a central role in the regulation of secretory and cytoskeletal responses in antigen-stimulated mast cells. In this study, we examine the kinetics and mechanism of Rac and Cdc42 activation in the rat basophilic leukemia RBL-2H3 cells. The activation kinetics of both Rac and Cdc42 show a biphasic profile, consisting of an early transient peak at 1,min and a late sustained activation phase at 20,40,min. The inhibition of phospholipase,C (PLC), causes a twofold increase in Rac and Cdc42 activation that coincides with a dramatic production of atypical filopodia-like structures. Inhibition of protein kinase,C using bisindolylmaleimide mimics the effect of PLC, inhibition on Rac activation, but not on Cdc42 activation. In contrast, depletion of intracellular calcium leads to a complete inhibition of the early activation peak of both Rac and Cdc42, without significant effects on the late sustained activation. These data suggest that PLC, is involved in a negative feedback loop that leads to the inhibition of Rac and Cdc42. They also suggest that the presence of intracellular calcium is a prerequisite for both Rac and Cdc42 activation. [source] Dock4 regulates dendritic development in hippocampal neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2008Shuhei Ueda Abstract Dendrite development is required for establishing proper neuronal connectivity. Rho-family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up-regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C-terminal Crk-binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. © 2008 Wiley-Liss, Inc. [source] A differential role of the platelet ADP receptors P2Y1 and P2Y12 in Rac activationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2005C. SOULET Summary., The dynamics of the actin cytoskeleton, largely controlled by the Rho family of small GTPases (Rho, Rac and Cdc42), is critical for the regulation of platelet responses such as shape change, adhesion, spreading and aggregation. Here, we investigated the role of adenosine diphosphate (ADP), a major co-activator of platelets, on the activation of Rac. ADP rapidly activated Rac in a dose-dependent manner and independently of GPIIb/IIIa and phosphoinositide 3-kinase. ADP alone, used as a primary agonist, activated Rac and its effector PAK via its P2Y1 receptor, through a Gq -dependent pathway and independently of P2Y12. The P2Y12 receptor appeared unable to activate the GTPase per se as also observed for the adenosine triphosphate receptor P2X1. Conversely, secreted ADP strongly potentiated Rac activation induced by Fc,RIIa clustering or TRAP via its P2Y12 receptor, the target of antithrombotic thienopyridines. Stimulation of the ,2A -adrenergic receptor/Gz pathway by epinephrine was able to replace the P2Y12/Gi -mediated pathway to amplify Rac activation by Fc,RIIa or by the thrombin receptor PAR-1. This co-activation appeared necessary to reach a full stimulation of Rac as well as PAK activation and actin polymerization and was blocked by a G-protein ,, subunits scavenger peptide. [source] | ||||||||||