PUBLICATION

FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology

Authors
Yasuda-Yamahara, M., Rogg, M., Frimmel, J., Trachte, P., Helmstaedter, M., Schroder, P., Schiffer, M., Schell, C., Huber, T.B.
ID
ZDB-PUB-190131-8
Date
2018
Source
Matrix biology : journal of the International Society for Matrix Biology   68-69: 263-279 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Cell Movement
  • Zebrafish
  • Drosophila
  • Mice
  • Animals
  • Proteomics
  • Actins/metabolism*
  • Focal Adhesions/metabolism*
  • Actomyosin/metabolism
  • Extracellular Matrix/metabolism
  • Cell Adhesion
  • Podocytes/cytology*
  • Podocytes/metabolism
  • Podocytes/physiology
  • Cell Membrane/physiology*
  • Gene Knockout Techniques
  • Disease Models, Animal
  • Humans
  • Membrane Proteins/genetics*
  • Membrane Proteins/metabolism*
  • Neoplasm Proteins/genetics*
  • Neoplasm Proteins/metabolism*
(all 22)
PubMed
29337051 Full text @ Matrix Biol.
Abstract
Simplification and retraction of podocyte protrusions, generally termed as foot process effacement, is a uniform pathological pattern observed in the majority of glomerular disease, including focal segmental glomerulosclerosis. However, it is still incompletely understood how the interaction of cortical actin structures, actomyosin contractility and focal adhesions, is being orchestrated to control foot process morphology in health and disease. By uncovering the functional role of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now evidence, how cell-extracellular matrix (ECM) interactions modulate membrane tension and actomyosin contractility. A genetic modeling approach was applied by deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified human podocytes. Loss of FERMT2 results in altered cortical actin composition, cell cortex destabilization associated with plasma membrane blebbing and a remodeling of focal adhesions. We further show that FERMT2 knockout podocytes have high levels of RhoA activation and concomitantly increased actomyosin contractility. Inhibition of actomyosin tension reverses the membrane blebbing phenotype. Thus, our findings establish a direct link between cell-matrix adhesions, cortical actin structures and plasma membrane tension allowing to better explain cell morphological changes in foot process effacement.
Genes / Markers
Figures
Figure Gallery (1 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
lri500Tg + MO3-fermt2standard conditionsDay 5
lri500Tg + MO3-fermt2standard conditionsDay 5
1 - 2 of 2
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
lri500TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    fermt2MO3-fermt2MRPHLNO
    1 - 1 of 1
    Show
    Fish
    Fish
    lri500Tg + MO3-fermt2
    1 - 1 of 1
    Show
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
    Show
    Mapping
    No data available
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    Citation
    Yasuda-Yamahara, M., Rogg, M., Frimmel, J., Trachte, P., Helmstaedter, M., Schroder, P., Schiffer, M., Schell, C., Huber, T.B. (2018) FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology. Matrix biology : journal of the International Society for Matrix Biology. 68-69:263-279.