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The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are A Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
2019 (English)In: CELLS, ISSN 2073-4409, Vol. 8, no 7, article id 759Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 8, no 7, article id 759
Keywords [en]
fast-cycling, Rho GTPases, Cdc42, Rac, filopodia, actin
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-393133DOI: 10.3390/cells8070759ISI: 000478902000023PubMedID: 31330900OAI: oai:DiVA.org:uu-393133DiVA, id: diva2:1353781
Funder
Swedish Cancer Society, CAN 2018/0419Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved

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