IQGAP-related protein DGAP1 mediates signaling to the actin cytoskeleton as an effector and a sequestrator of Rac1 GTPases

Proteins are typically categorized into protein families based on their domain organization. Yet, evolutionarily unrelated proteins can also be grouped together according to their common functional roles. Sequestering proteins constitute one such functional class, acting as macromolecular buffers an...

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Published in:Cellular and molecular life sciences : CMLS 2014-08, Vol.71 (15), p.2775-2785
Main Authors: Filić, Vedrana, Marinović, Maja, Faix, Jan, Weber, Igor
Format: Article
Language:English
Subjects:
actin
Actin Cytoskeleton - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell adhesion & migration
Cell Biology
Cell Movement
Cell Polarity
Cytoskeleton
Dictyostelium
Dictyostelium - cytology
Dictyostelium - metabolism
Enzymes
guanosinetriphosphatase
Life Sciences
Microfilament Proteins - metabolism
microfilaments
Molecular biology
polymerization
Proteins
Protozoan Infections - parasitology
Protozoan Proteins - metabolism
rac1 GTP-Binding Protein - metabolism
scaffolding proteins
Signal Transduction
Visions and Reflections
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Summary:Proteins are typically categorized into protein families based on their domain organization. Yet, evolutionarily unrelated proteins can also be grouped together according to their common functional roles. Sequestering proteins constitute one such functional class, acting as macromolecular buffers and serving as an intracellular reservoir ready to release large quantities of bound proteins or other molecules upon appropriate stimulation. Another functional protein class comprises effector proteins, which constitute essential components of many intracellular signal transduction pathways. For instance, effectors of small GTP-hydrolases are activated upon binding a GTP-bound GTPase and thereupon participate in downstream interactions. Here we describe a member of the IQGAP family of scaffolding proteins, DGAP1 from Dictyostelium, which unifies the roles of an effector and a sequestrator in regard to the small GTPase Rac1. Unlike classical effectors, which bind their activators transiently leading to short-lived signaling complexes, interaction between DGAP1 and Rac1-GTP is stable and induces formation of a complex with actin-bundling proteins cortexillins at the back end of the cell. An oppositely localized Rac1 effector, the Scar/WAVE complex, promotes actin polymerization at the cell front. Competition between DGAP1 and Scar/WAVE for the common activator Rac1-GTP might provide the basis for the oscillatory re-polarization typically seen in randomly migrating Dictyostelium cells. We discuss the consequences of the dual roles exerted by DGAP1 and Rac1 in the regulation of cell motility and polarity, and propose that similar signaling mechanisms may be of general importance in regulating spatiotemporal dynamics of the actin cytoskeleton by small GTPases.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-014-1606-3