Rho GTPases and their role in organizing the actin cytoskeleton

ST Sit, E Manser - Journal of cell science, 2011 - journals.biologists.com
ST Sit, E Manser
Journal of cell science, 2011journals.biologists.com
Cells receive extracellular stimuli in various ways: in the form of soluble molecules (growth
factors, cytokines and hormones) that interact with cell-surface receptors; from adhesive
interactions with the extracellular matrix; and from cell–cell adhesions. These stimuli act to
generate changes in the actin cytoskeleton at specific sites (see Poster), primarily through
Rho proteins. Local guanine-nucleotideexchange factors (GEFs) or GTPase-activating
proteins (GAPs) serve to upregulate or downregulate the active levels of membranebound …
Cells receive extracellular stimuli in various ways: in the form of soluble molecules (growth factors, cytokines and hormones) that interact with cell-surface receptors; from adhesive interactions with the extracellular matrix; and from cell–cell adhesions. These stimuli act to generate changes in the actin cytoskeleton at specific sites (see Poster), primarily through Rho proteins. Local guanine-nucleotideexchange factors (GEFs) or GTPase-activating proteins (GAPs) serve to upregulate or downregulate the active levels of membranebound Rho proteins. In humans,~ 20 Rho GTPases exist, of which Rho, Rac and Cdc42 remain the best studied (for a review, see Heasman and Ridley, 2008). Once activated, Rho GTPases bind to a variety of effectors, including protein kinases (Zhao and Manser, 2005) and some actin-binding proteins. These directly or indirectly affect the local assembly or disassembly of filamentous (F)-actin. The pathways downstream of Rho that impinge on actin are the subject of this Cell Science at a Glance article. For each cellular structure in a ‘typical’adherent cell, we have incorporated information on the specific role of Rho effectors.
Some background on these effectors, their regulation and their actin-related roles is provided in the text. This article does not consider the role of Rho proteins in mediating changes in actin dynamics during the cell cycle [for more information on this topic, see Villalonga and Ridley (Villalonga and Ridley, 2006)] or in the specialized podosome or invadopodia structures (for reviews, see Buccione et al., 2004; Linder, 2007; Albiges-Rizo et al., 2009).
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