A Rho GTPase Signal Treadmill Backs a Contractile Array

Abstract

Contractile arrays of actin filaments (F-actin) and myosin-2 power diverse biological processes. Contractile array formation is stimulated by the Rho GTPases Rho and Cdc42; after assembly, array movement is thought to result from contraction itself. Contractile array movement and GTPase activity were analyzed during cellular wound repair, in which arrays close in association with zones of Rho and Cdc42 activity. Remarkably, contraction suppression prevents translocation of F-actin and myosin-2 without preventing array or zone closure. Closure is driven by an underlying “signal treadmill” in which the GTPases are preferentially activated at the leading edges and preferentially lost from the trailing edges of their zones. Treadmill organization requires myosin-2 powered contraction and F-actin turnover. Thus, directional gradients in Rho GTPase turnover impart directional information to contractile arrays and proper functioning of these gradients is dependent on both contraction and F-actin turnover.

Single cell wound generates electric current circuit and cell membrane potential variations that requires calcium influx

“…2 Recent research has provided significant insights into the directional movement of vesicles, growth of cytoskeleton, and directional signaling of small GTPases. 3 An actomyosin contractile ring (controlled by concentric zones of the small GTPases Rho and Cdc42) is formed and closes to heal the cortical cytoskeleton. 3,4 The mechanisms by which vesicles move to the wound site, and how actomyosin ring contraction is initiated and controlled, are not well understood.…”

“…3 An actomyosin contractile ring (controlled by concentric zones of the small GTPases Rho and Cdc42) is formed and closes to heal the cortical cytoskeleton. 3,4 The mechanisms by which vesicles move to the wound site, and how actomyosin ring contraction is initiated and controlled, are not well understood. Bement et al demonstrated that the centripetal signaling towards the center of the membrane breach does not depend on a myosin contraction ring.…”

S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells

“…Absence of either of these proteins prevents F-actin buildup following injury and prevents PMR, similar to the drugs that alter actin polymerization or depolymerization. 13,74 Cortical F-actin deploymerization around the injury site is followed by the recruitment of ANXA1 at the damaged PM and excision of this damaged membrane. Loss of ANXA2 and S100A11 and pharmacological inhibition of F-actin buildup prevent PMR by blocking excision of the damaged part of the PM marked by ANXA1.…”

Plasma membrane repair provides a new strategy for targeting metastatic cancer cells

“…This function of S100A11-ANXA2 complex is in agreement with work showing individual interactions of S100A11 and ANXA2 proteins with the actin cytoskeleton [46,47] . The important role of actin dynamics in this process is further supported by inhibition of PMR by drugs that block actin polymerization or depolymerization [48] . We present evidence that this is due to the role of membrane-associated cortical actin cytoskeleton in maintaining cell membrane stability [1] .…”