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

2016 ◽  
Author(s):  
Cibele V. Falkenberg ◽  
Evren U. Azeloglu ◽  
Mark Stothers ◽  
Thomas J. Deerinck ◽  
Yibang Chen ◽  
...  

AbstractThe kidney podocyte’s function depends on its distinctive morphology. Each podocyte has fingerlike 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 heterogeneity of cytoskeletal dynamics resulting in the emergence of progressive and chaotic loss of foot processes. While global enhancement of Rac1 may result in stronger bundles, the spatial simulations showed that even transient local heterogeneities in polymerization could have dramatic consequences in the stability of multiple foot processes. We conclude that the podocyte morphology optimized for filtration contains intrinsic fragility whereby local imbalances in biochemical and biophysical reactions lead to morphological changes associated with glomerular pathophysiology.

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1700 ◽  
Author(s):  
Judith Blaine ◽  
James Dylewski

Podocytes are an integral part of the glomerular filtration barrier, a structure that prevents filtration of large proteins and macromolecules into the urine. Podocyte function is dependent on actin cytoskeleton regulation within the foot processes, structures that link podocytes to the glomerular basement membrane. Actin cytoskeleton dynamics in podocyte foot processes are complex and regulated by multiple proteins and other factors. There are two key signal integration and structural hubs within foot processes that regulate the actin cytoskeleton: the slit diaphragm and focal adhesions. Both modulate actin filament extension as well as foot process mobility. No matter what the initial cause, the final common pathway of podocyte damage is dysregulation of the actin cytoskeleton leading to foot process retraction and proteinuria. Disruption of the actin cytoskeleton can be due to acquired causes or to genetic mutations in key actin regulatory and signaling proteins. Here, we describe the major structural and signaling components that regulate the actin cytoskeleton in podocytes as well as acquired and genetic causes of actin dysregulation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Keiichi Kataoka ◽  
Hironori Fujita ◽  
Mutsumi Isa ◽  
Shimpei Gotoh ◽  
Akira Arasaki ◽  
...  

AbstractMorphological variations in human teeth have long been recognized and, in particular, the spatial and temporal distribution of two patterns of dental features in Asia, i.e., Sinodonty and Sundadonty, have contributed to our understanding of the human migration history. However, the molecular mechanisms underlying such dental variations have not yet been completely elucidated. Recent studies have clarified that a nonsynonymous variant in the ectodysplasin A receptor gene (EDAR370V/A; rs3827760) contributes to crown traits related to Sinodonty. In this study, we examined the association between theEDARpolymorphism and tooth root traits by using computed tomography images and identified that the effects of theEDARvariant on the number and shape of roots differed depending on the tooth type. In addition, to better understand tooth root morphogenesis, a computational analysis for patterns of tooth roots was performed, assuming a reaction–diffusion system. The computational study suggested that the complicated effects of theEDARpolymorphism could be explained when it is considered that EDAR modifies the syntheses of multiple related molecules working in the reaction–diffusion dynamics. In this study, we shed light on the molecular mechanisms of tooth root morphogenesis, which are less understood in comparison to those of tooth crown morphogenesis.


2011 ◽  
Vol 208 (5) ◽  
pp. 1055-1068 ◽  
Author(s):  
Bebhinn Treanor ◽  
David Depoil ◽  
Andreas Bruckbauer ◽  
Facundo D. Batista

Signaling microclusters are a common feature of lymphocyte activation. However, the mechanisms controlling the size and organization of these discrete structures are poorly understood. The Ezrin-Radixin-Moesin (ERM) proteins, which link plasma membrane proteins with the actin cytoskeleton and regulate the steady-state diffusion dynamics of the B cell receptor (BCR), are transiently dephosphorylated upon antigen receptor stimulation. In this study, we show that the ERM proteins ezrin and moesin influence the organization and integrity of BCR microclusters. BCR-driven inactivation of ERM proteins is accompanied by a temporary increase in BCR diffusion, followed by BCR immobilization. Disruption of ERM protein function using dominant-negative or constitutively active ezrin constructs or knockdown of ezrin and moesin expression quantitatively and qualitatively alters BCR microcluster formation, antigen aggregation, and downstream BCR signal transduction. Chemical inhibition of actin polymerization also altered the structure and integrity of BCR microclusters. Together, these findings highlight a crucial role for the cortical actin cytoskeleton during B cell spreading and microcluster formation and function.


2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Kamrun Nahar Keya ◽  
Md. Kamrujjaman ◽  
Md. Shafiqul Islam

AbstractIn this paper, we consider a reaction–diffusion model in population dynamics and study the impact of different types of Allee effects with logistic growth in the heterogeneous closed region. For strong Allee effects, usually, species unconditionally die out and an extinction-survival situation occurs when the effect is weak according to the resource and sparse functions. In particular, we study the impact of the multiplicative Allee effect in classical diffusion when the sparsity is either positive or negative. Negative sparsity implies a weak Allee effect, and the population survives in some domain and diverges otherwise. Positive sparsity gives a strong Allee effect, and the population extinct without any condition. The influence of Allee effects on the existence and persistence of positive steady states as well as global bifurcation diagrams is presented. The method of sub-super solutions is used for analyzing equations. The stability conditions and the region of positive solutions (multiple solutions may exist) are presented. When the diffusion is absent, we consider the model with and without harvesting, which are initial value problems (IVPs) and study the local stability analysis and present bifurcation analysis. We present a number of numerical examples to verify analytical results.


2019 ◽  
Vol 29 (11) ◽  
pp. 1950144 ◽  
Author(s):  
Zuolin Shen ◽  
Junjie Wei

In this paper, we consider the dynamics of a delayed reaction–diffusion mussel-algae system subject to Neumann boundary conditions. When the delay is zero, we show the existence of positive solutions and the global stability of the boundary equilibrium. When the delay is not zero, we obtain the stability of the positive constant steady state and the existence of Hopf bifurcation by analyzing the distribution of characteristic values. By using the theory of normal form and center manifold reduction for partial functional differential equations, we derive an algorithm that determines the direction of Hopf bifurcation and the stability of bifurcating periodic solutions. Finally, some numerical simulations are carried out to support our theoretical results.


2016 ◽  
Vol 26 (08) ◽  
pp. 1650135 ◽  
Author(s):  
C. A. Cardoso ◽  
J. A. Langa ◽  
R. Obaya

In this paper, we describe in detail the global and cocycle attractors related to nonautonomous scalar differential equations with diffusion. In particular, we investigate reaction–diffusion equations with almost-periodic coefficients. The associated semiflows are strongly monotone which allow us to give a full characterization of the cocycle attractor. We prove that, when the upper Lyapunov exponent associated to the linear part of the equations is positive, the flow is persistent in the positive cone, and we study the stability and the set of continuity points of the section of each minimal set in the global attractor for the skew product semiflow. We illustrate our result with some nontrivial examples showing the richness of the dynamics on this attractor, which in some situations shows internal chaotic dynamics in the Li–Yorke sense. We also include the sublinear and concave cases in order to go further in the characterization of the attractors, including, for instance, a nonautonomous version of the Chafee–Infante equation. In this last case we can show exponentially forward attraction to the cocycle (pullback) attractors in the positive cone of solutions.


2014 ◽  
Vol 20 (1) ◽  
pp. 55-76 ◽  
Author(s):  
Tom Froese ◽  
Nathaniel Virgo ◽  
Takashi Ikegami

Due to recent advances in synthetic biology and artificial life, the origin of life is currently a hot topic of research. We review the literature and argue that the two traditionally competing replicator-first and metabolism-first approaches are merging into one integrated theory of individuation and evolution. We contribute to the maturation of this more inclusive approach by highlighting some problematic assumptions that still lead to an ximpoverished conception of the phenomenon of life. In particular, we argue that the new consensus has so far failed to consider the relevance of intermediate time scales. We propose that an adequate theory of life must account for the fact that all living beings are situated in at least four distinct time scales, which are typically associated with metabolism, motility, development, and evolution. In this view, self-movement, adaptive behavior, and morphological changes could have already been present at the origin of life. In order to illustrate this possibility, we analyze a minimal model of lifelike phenomena, namely, of precarious, individuated, dissipative structures that can be found in simple reaction-diffusion systems. Based on our analysis, we suggest that processes on intermediate time scales could have already been operative in prebiotic systems. They may have facilitated and constrained changes occurring in the faster- and slower-paced time scales of chemical self-individuation and evolution by natural selection, respectively.


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