The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System
The Rho GTPases comprise a subfamily of the Ras superfamily of small GTPases. Their importance in regulation of cell morphology and cell migration is well characterized. According to the prevailing paradigm, Cdc42 regulates the formation of filopodia, Rac1 regulates the formation of lamellipodia, an...
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doaj-8e659fef8e4a4ca48006291b0be042272020-11-25T01:55:22ZengMDPI AGCells2073-44092019-07-018775910.3390/cells8070759cells8070759The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament SystemPontus Aspenström0Rudbeck Laboratory, Department of Immunology, Genetics and Pathology (IGP), Uppsala University, SE 751 85 Uppsala, SwedenThe Rho GTPases comprise a subfamily of the Ras superfamily of small GTPases. Their importance in regulation of cell morphology and cell migration is well characterized. According to the prevailing paradigm, Cdc42 regulates the formation of filopodia, Rac1 regulates the formation of lamellipodia, and RhoA triggers the assembly of focal adhesions. However, this scheme is clearly an oversimplification, as the Rho subfamily encompasses 20 members with diverse effects on a number of vital cellular processes, including cytoskeletal dynamics and cell proliferation, migration, and invasion. This article highlights the importance of the catalytic activities of the classical Rho GTPases Cdc42 and Rac1, in terms of their specific effects on the dynamic reorganization of the actin filament system. GTPase-deficient mutants of Cdc42 and Rac1 trigger the formation of broad lamellipodia and stress fibers, and fast-cycling mutations trigger filopodia formation and stress fiber dissolution. The filopodia response requires the involvement of the formin family of actin nucleation promotors. In contrast, the formation of broad lamellipodia induced by GTPase-deficient Cdc42 and Rac1 is mediated through Arp2/3-dependent actin nucleation.https://www.mdpi.com/2073-4409/8/7/759fast-cyclingRho GTPasesCdc42Racfilopodiaactin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pontus Aspenström |
spellingShingle |
Pontus Aspenström The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System Cells fast-cycling Rho GTPases Cdc42 Rac filopodia actin |
author_facet |
Pontus Aspenström |
author_sort |
Pontus Aspenström |
title |
The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System |
title_short |
The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System |
title_full |
The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System |
title_fullStr |
The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System |
title_full_unstemmed |
The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System |
title_sort |
intrinsic gdp/gtp exchange activities of cdc42 and rac1 are critical determinants for their specific effects on mobilization of the actin filament system |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2019-07-01 |
description |
The Rho GTPases comprise a subfamily of the Ras superfamily of small GTPases. Their importance in regulation of cell morphology and cell migration is well characterized. According to the prevailing paradigm, Cdc42 regulates the formation of filopodia, Rac1 regulates the formation of lamellipodia, and RhoA triggers the assembly of focal adhesions. However, this scheme is clearly an oversimplification, as the Rho subfamily encompasses 20 members with diverse effects on a number of vital cellular processes, including cytoskeletal dynamics and cell proliferation, migration, and invasion. This article highlights the importance of the catalytic activities of the classical Rho GTPases Cdc42 and Rac1, in terms of their specific effects on the dynamic reorganization of the actin filament system. GTPase-deficient mutants of Cdc42 and Rac1 trigger the formation of broad lamellipodia and stress fibers, and fast-cycling mutations trigger filopodia formation and stress fiber dissolution. The filopodia response requires the involvement of the formin family of actin nucleation promotors. In contrast, the formation of broad lamellipodia induced by GTPase-deficient Cdc42 and Rac1 is mediated through Arp2/3-dependent actin nucleation. |
topic |
fast-cycling Rho GTPases Cdc42 Rac filopodia actin |
url |
https://www.mdpi.com/2073-4409/8/7/759 |
work_keys_str_mv |
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