2024 | Bement, WM, Goryachev, AB, Miller, AL & von Dassow, G
The Rho GTPases—Rho, Rac, and CDC42—are small GTP-binding proteins that regulate fundamental cellular processes such as cell locomotion, division, and morphogenesis by modulating the cytoskeleton. This regulation involves the activation and inactivation of Rho GTPases, which are controlled by GEFs (guanine nucleotide exchange factors) and GAPs (guanine nucleotide dissociation inhibitors). While the classical view suggests a linear activation-inactivation process, recent studies using live cell imaging, modeling, and experimental manipulations reveal that Rho GTPase activation and inactivation are often coupled in space and time through positive and negative feedback loops. This coupling enables self-organization of Rho GTPases into various spatio-temporal cortical patterns, including static clusters, oscillatory pulses, traveling wave trains, and ring-like waves. These patterns are essential for diverse cellular functions, such as polarized growth, pulsatile contractions, traveling waves of actin assembly, and cell junction maintenance. The self-organization of Rho GTPases is driven by the interplay of positive and negative feedback loops, which can be direct, effector-based, or effector target-based. The diversity of these feedback mechanisms allows for a wide range of self-organized patterns, contributing to the complexity of cellular processes.The Rho GTPases—Rho, Rac, and CDC42—are small GTP-binding proteins that regulate fundamental cellular processes such as cell locomotion, division, and morphogenesis by modulating the cytoskeleton. This regulation involves the activation and inactivation of Rho GTPases, which are controlled by GEFs (guanine nucleotide exchange factors) and GAPs (guanine nucleotide dissociation inhibitors). While the classical view suggests a linear activation-inactivation process, recent studies using live cell imaging, modeling, and experimental manipulations reveal that Rho GTPase activation and inactivation are often coupled in space and time through positive and negative feedback loops. This coupling enables self-organization of Rho GTPases into various spatio-temporal cortical patterns, including static clusters, oscillatory pulses, traveling wave trains, and ring-like waves. These patterns are essential for diverse cellular functions, such as polarized growth, pulsatile contractions, traveling waves of actin assembly, and cell junction maintenance. The self-organization of Rho GTPases is driven by the interplay of positive and negative feedback loops, which can be direct, effector-based, or effector target-based. The diversity of these feedback mechanisms allows for a wide range of self-organized patterns, contributing to the complexity of cellular processes.