Patterning of the cell cortex by Rho GTPases

Abstract

The Rho GTPases-Rho, Rac and CDC42-are small GTP-binding proteins that regulate basic biological processes such as cell locomotion, cell division and morphogenesis by promoting cytoskeleton-based changes in the cell cortex. This regulation results from active (GTP-bound) Rho GTPases stimulating target proteins that in turn promote actin assembly and myosin-2-based contraction to pattern the organization of the cortex. This basic regulatory scheme, well-supported by in vitro studies, led to the natural assumption that Rho GTPases function in vivo in an essentially linear matter, with a given process being initiated by GTPase activation and terminated by GTPase inactivation. However, a growing body of evidence based on live cell imaging, modelling, and experimental manipulation indicates that Rho GTPase activation and inactivation are often tightly coupled in space and time via signalling circuits and networks based on positive and negative feedback. In this Review, we present and discuss this evidence, and we address one of the fundamental consequences of coupled activation and inactivation: the ability of the Rho GTPases to self-organize. We discuss how Rho GTPase self-organization results in the formation of diverse spatio-temporal cortical patterns such as static clusters, oscillatory pulses, traveling wave trains, and ring-like waves. Finally, we discuss the advantages of Rho GTPase self-organization and pattern formation for cell function.

Mevalonate metabolites boost aged oocyte quality through small GTPases prenylation

“…7e,f). The Arp2/3 complex can be activated by the CDC42/N-WASP or RAC1-WAVE2 signalling pathways to promote the cortical F-actin assembly in oocytes 9,33 . Reciprocal coimmunoprecipitation analysis further con rmed the endogenous interaction between CDC42 with N-WASP and the Arp2/3 complex, as well as the interaction between endogenous RAC1, WAVE2 and the Arp2/3 complex.…”

“…Mevalonate (MVA) pathway is crucial for cholesterol synthesis and regulates multiple cellular processes through protein prenylation, a lipidic modi cation that facilitates the anchoring of proteins to cell membranes 8 . Small GTPases could be prenylated and regulate cell division and morphogenesis by promoting cytoskeleton organization and cortex formation 9 . Recently, we reported that abnormal metabolism of the MVA pathway in granulosa cells (GCs) is an important contributing factor to meiotic defects and aneuploidy and MVA supplementation increases normal meiosis in aged oocyte 10 .…”

A short guide to the tight junction

“…Finally, both in vivo Xenopus studies and in vitro analyses of mammalian epithelia show that activities of Rho GTPases and ROCKs are critical for the repair of junctional damage and for TJ remodeling to maintain barrier function ( Varadarajan et al, 2019 ). Studies in Xenopus also show a role for mechanosensitive Ca 2+ flashes and the RhoA GEF p115RhoGEF (also known as Arhgef1) in promoting RhoA activation to repair damaged TJs and thus maintaining barrier function ( Varadarajan et al, 2019 ; Bement et al, 2024 ).…”

Editorial: Self-organizing and excitable signaling networks in cell biology

“…Waves of F-actin and Rho activation have also been observed in the eggs and embryonic cells of frogs and starfish. In these cells, cortical waves are regulated by mitotic spindles and are implicated in cytokinesis ( Bement et al, 2024 ). Sepaniac et al studied how actin waves respond to wounding and change over the course of embryonic development in the Xenopus embryo.…”