Rho GTPase Function in Cell Morphogenesis


Cell morphogenesis is the development of a specific cell morphology, which includes the acquisition of cell shape, cell polarity, cell–cell and cell–ECM (extracellular matrix) contacts. Cell morphogenesis is dependent on the interaction of the cell with its environment and therefore not a cell autonomous process. Crucial for cell morphogenesis is the regulation of the actin cytoskeleton. Furthermore, regulation of gene expression and activation of different intracellular signalling pathways contribute to cell morphogenesis. Rho guanosine triphosphatases (GTPases) are master regulators of the actin cytoskeleton, which affects cell shape and the position of integrins and cadherins, actin cytoskeleton attached cell surface receptors. In addition, Rho GTPases regulate endocytosis, vesicle transport, secretion and gene expression. Not surprisingly, therefore, this family of molecules was found to be particularly important for cell morphogenesis.

Key Concepts:

  • Rho GTPases are signal integrators.

  • Rho GTPases have overlapping functions.

  • Rho GTPases regulate cell shape by controlling remodelling of the actin cytoskeleton.

  • Cdc42 regulates different aspects of cell polarity in a cell type‐specific manner.

  • Rho GTPases regulate cell adhesion to the extracellular matrix and to other cells.

Keywords: Rho GTPases; cell morphogenesis; cell shape; cell polarity; cell–cell adhesion; cell ECM adhesion

Figure 1.

Rho GTPase cycle. Rho GTPases cycle between an active GTP‐bound and an inactive GDP‐bound form. Activation is catalysed by GEFs, whereas inactivation by hydrolysis of GTP is facilitated by GAPs. GDIs sequestrate inactive Rho GTPases. Only in their GTP‐bound form, Rho GTPases can interact with effectors and initiate biological effects.

Figure 2.

Rho GTPase regulation of lamellipodia and filopodia formation. Membrane‐bound, activated Rho GTPases initiate the formation of filopodia involving mDia2, IRSp53 and N‐WASP and promote lamellipodia by interaction with the WAVE complex (green circles). The WAVE complex in turn binds to the Arp2/3 complex (red ovals), which nucleates actin filaments. The WAVE complex can leave the filament and become replaced by VASP (following the hypothetical model of Urban et al. ). Rho GTPases control degradation of filopodia and lamellipodia by regulating the activity of the actin filament severing cofilin.



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Further Reading

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Pedersen, Esben, and Brakebusch, Cord(Nov 2010) Rho GTPase Function in Cell Morphogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022525]