Abstract
Many cell regulatory systems implicate significant nonlinearity and redundancy among components. The regulatory network governing the formation of lamellipodial and lamellar actin structures is prototypical of such a system, containing tens of actin-nucleating and -modulating molecules with strong functional overlap. Due to instantaneous compensation, the strategy of phenotyping the system response to perturbation of individual components provides limited information on the roles the targeted component plays in the unperturbed system. Accordingly, despite the very rich data on lamellipoidial actin assembly, we have an incomplete understanding of how individual actin regulators contribute to lamellipodial dynamics. Here, we present a case study of perturbation-free reconstruction of cause-effect relations among actin regulators, applying the framework of Granger-causal inference to constitutive image fluctuations that indicate regulator recruitment and dissociation. Our analysis defines distinct active zones for actin regulators within the lamellipodia and lamella and establishes actin-dependent and actin-independent causal relations with actin filament assembly and edge motion. We demonstrate the specificity and sensitivity of the analysis and propose that edge motion is driven by assembly of two independently operating actin filament structures.
Competing Interest Statement
The authors have declared no competing interest.