A versatile cortical pattern-forming circuit based on Rho, F-actin, Ect2, and RGA-3/4

Abstract

Many cells can generate complementary traveling waves of actin filaments (F-actin) and cytoskeletal regulators. This phenomenon, termed cortical excitability, results from coupled positive and negative feedback loops of cytoskeletal regulators. The nature of these feedback loops, however, remains poorly understood. We assessed the role of the Rho GAP RGA-3/4 in the cortical excitability that accompanies cytokinesis in both frog and starfish. RGA-3/4 localizes to the cytokinetic apparatus, “chases” Rho waves in an F-actin–dependent manner, and when coexpressed with the Rho GEF Ect2, is sufficient to convert the normally quiescent, immature Xenopus oocyte cortex into a dramatically excited state. Experiments and modeling show that changing the ratio of RGA-3/4 to Ect2 produces cortical behaviors ranging from pulses to complex waves of Rho activity. We conclude that RGA-3/4, Ect2, Rho, and F-actin form the core of a versatile circuit that drives a diverse range of cortical behaviors, and we demonstrate that the immature oocyte is a powerful model for characterizing these dynamics.

Testing models of cell cortex wave generation by Rho GTPases

“…Therefore, it remains largely unknown how membrane accumulation of Rho GTPases (i.e., Rho membrane enrichment) is related to Rho activity. Here we dissect the dynamics of RhoA by simultaneously imaging both total RhoA and active RhoA in the regime of acute cortical excitability 2 , characterized by pronounced waves of Rho activity and F-actin polymerization [3][4][5] . We find that within nascent waves, accumulation of active RhoA precedes that of total RhoA, and we exploit this finding to distinguish between two popular theoretical models previously used to explain propagating cortical Rho waves.…”

Plasma membrane topography governs the 3D dynamic localization of IgM B cell antigen receptor clusters

“…Interestingly, the 3D trajectory of IgM‐BCR clusters on smooth regions of LatA‐treated cells still seems to form a network of polygonal patterns. Molecules such as phosphoinositides or Rho GTPases display dynamic molecular patterns at the cell cortex as a result of positive and negative feedback loops acting on them (Koch & Meinhardt, 1994 ; Bement et al , 2015 ; Xiong et al , 2016 ; Michaud et al , 2022 ). It is conceivable that such molecular patterns may form the basis of the network‐forming ridges by recruiting curvature‐inducing proteins and actin nucleation‐promoting factors (Miki et al , 2000 ; Ho et al , 2004 ; Fricke et al , 2009 ; de Kreuk & Hordijk, 2012 ; Suetsugu & Gautreau, 2012 ; Becalska et al , 2013 ; Saengsawang et al , 2013 ; Aspenström, 2014 ; Suetsugu et al , 2014 ; Simunovic et al , 2017 ; Wu et al , 2018 ).…”

A dynamic partitioning mechanism polarizes membrane protein distribution

“…Dynamic partitioning mechanism that we establish here (Figure 7G) is distinct from multiple mechanisms that have been previously proposed to explain symmetry breaking which bring about polarization or traveling waves on the cell cortex. Inaddition to the examples of self-organizing patterns in Dictyostelium mentioned above, “shuttling” or relocalization of proteins between the cytosol and membrane has been shown to drive pattern formation during the propagation of Hem-1 (of Scar/WAVE complex) waves in migrating neutrophils 56 , Cdc42/FBP17 waves in tumor mast cells 20, 73 , Actin-polymerization/Rho-actvity/RhoGAP (RGA-3/4) waves in Xenopus (frog) eggs and Patiria (starfish) embryo 74, 75 , Actin-polymerization/PI3K waves in epithelial breast cancer cells 76 , myosin IB/actin polymerization waves in Dictyostelium 57 as well as waves of multiple signaling components in Dictyostelium 25, 31, 45 . In distinction to shuttling, “fence and picket” models of membrane organization have been proposed to explain polarized distributions in the membrane 21, 22 .…”