Chaotic propagation of spatial cytoskeletal instability modulates integrity of podocyte foot processes Article Swipe
Cibele V. Falkenberg
,
Evren U. Azeloglu
,
Mark Stothers
,
Thomas J. Deerinck
,
Yibang Chen
,
John Cijiang He
,
Mark H. Ellisman
,
James Hone
,
Ravi Iyengar
,
Leslie M. Loew
·
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1101/065839
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1101/065839
The 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.
Related Topics
Concepts
Cytoskeleton
Podocyte
RHOA
Actin
Actin cytoskeleton
Biophysics
Biology
Chemistry
Cell biology
Cell
Kidney
Signal transduction
Biochemistry
Endocrinology
Proteinuria
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/065839
- https://www.biorxiv.org/content/biorxiv/early/2016/07/26/065839.1.full.pdf
- OA Status
- green
- References
- 32
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2507977571
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2507977571Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/065839Digital Object Identifier
- Title
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Chaotic propagation of spatial cytoskeletal instability modulates integrity of podocyte foot processesWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2016Year of publication
- Publication date
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2016-07-26Full publication date if available
- Authors
-
Cibele V. Falkenberg, Evren U. Azeloglu, Mark Stothers, Thomas J. Deerinck, Yibang Chen, John Cijiang He, Mark H. Ellisman, James Hone, Ravi Iyengar, Leslie M. LoewList of authors in order
- Landing page
-
https://doi.org/10.1101/065839Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2016/07/26/065839.1.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2016/07/26/065839.1.full.pdfDirect OA link when available
- Concepts
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Cytoskeleton, Podocyte, RHOA, Actin, Actin cytoskeleton, Biophysics, Biology, Chemistry, Cell biology, Cell, Kidney, Signal transduction, Biochemistry, Endocrinology, ProteinuriaTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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32Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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