Molecular mechanism of autocatalytic Rho activation

Determine the molecular mechanisms that generate autocatalytic activation of Rho GTPase within the Ect2/Rho signaling network, clarifying how guanine nucleotide exchange factors such as Ect2 produce the effective nonlinear positive feedback used in models of Rho-GTP production in starfish oocytes and related systems.

Background

The optogenetic and modeling framework in the paper relies on an effective nonlinear term representing autocatalytic Rho activation to reproduce excitable Rho dynamics and resulting shape changes. Although the authors show that this term captures observed phenomena, they explicitly note that the underlying molecular mechanism remains incompletely characterized.

A recent structural paper on human Ect2 suggests a possible regulatory mechanism, but a comprehensive understanding of how Ect2 or other RhoGEFs implement positive feedback to Rho-GTP production is still lacking. Pinpointing this mechanism would refine biochemical models and improve quantitative predictions of chemo-mechanical cell behaviors.