Chaotic propagation of spatial cytoskeletal instability modulates integrity of podocyte foot processes

BioRxiv : the Preprint Server for Biology
Cibele V FalkenbergLeslie M Loew

Abstract

The function of the kidney podocyte depends on its distinctive morphology. Each podocyte has finger-like projections, called foot processes, that interdigitate with the processes of neighboring cells to form the glomerular filtration barrier. The integrity of foot process interactions depends on tight spatial control of the dynamics of the underlying actin cytoskeleton, which is regulated by the GTPases, Rac1 and RhoA. To understand how spatially-specific regulation of actin filament dynamics within foot processes controls local morphology, we used a combination of 3-D microscopy and dynamical models. We experimentally determined cell-cell interactions using serial blockface scanning electron microscopy and reconstructed a 3-D spatial representation of a podocyte. We developed a minimal dynamical system for regulation of the actin cytoskeleton; using this 3-D model, we determined how spatial reaction-diffusion dynamics can dysregulate actin bundling, leading to propagation of chaotic foot process effacement. Consistent with experimental observations, our simulations predicted that hyperactive RhoA could destabilize the cytoskeleton. Our simulations showed that deleterious mechanochemical stimuli could lead to local heterogeneit...Continue Reading

Related Concepts

Filtration
Projections and Predictions
Regulation of Biological Process
Actins
Diffusion Weighted Imaging
Science of Morphology
Spatial Distribution
FSCN1
Renal Glomerular Disease
Secondary Foot Process

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.