Control of the G-protein cascade dynamics by GDP dissociation inhibitors

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Title: Control of the G-protein cascade dynamics by GDP dissociation inhibitors
Authors: Nikonova, Elena
Tsyganov, Mikhail A.
Kolch, Walter
et al.
Permanent link: http://hdl.handle.net/10197/5022
Date: 2013
Abstract: A network of the Rho family GTPases, which cycle between inactive GDP-bound and active GTP-bound states, controls key cellular processes, including proliferation and migration. Activating and deactivating GTPase transitions are controlled by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and GDP dissociation inhibitors (GDIs) that sequester GTPases from the membrane to the cytoplasm. Here we show that a cascade of two Rho family GTPases, RhoA and Rac1, regulated by RhoGDI1, exhibits distinct modes of the dynamic behavior, including abrupt, bistable switches, excitable overshoot transitions and oscillations. The RhoGDI1 abundance and signal-induced changes in the RhoGDI1 affinity for GTPases control these different dynamics, enabling transitions from a single stable steady state to bistability, to excitable pulses and to sustained oscillations of GTPase activities. These RhoGDI1-controlled dynamic modes of RhoA and Rac1 activities form the basis of cell migration behaviors, including protrusion–retraction cycles at the leading edge of migrating cells.
Type of material: Journal Article
Publisher: The Royal Society of Chemistry
Copyright (published version): 2013 The Royal Society of Chemistry
Keywords: G-protein cascade;GDP dissociation inhibitors;RhoA;Rac1;cell migration behaviors
DOI: 10.1039/c3mb70152b
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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