scholarly journals The PKGIα/VASP pathway is involved in insulin- and high glucose-dependent regulation of albumin permeability in cultured rat podocytes

2020 ◽  
Vol 168 (6) ◽  
pp. 575-588
Author(s):  
Patrycja Rachubik ◽  
Maria Szrejder ◽  
Irena Audzeyenka ◽  
Dorota Rogacka ◽  
Michał Rychłowski ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
High Glucose ◽  
Principal Component ◽  
Glomerular Permeability ◽  
Filtration Barrier ◽  
Vasp Phosphorylation ◽  
High Insulin ◽  
Cytoskeleton Dynamics ◽  
Regulation Of Actin Cytoskeleton

Abstract Podocytes, the principal component of the glomerular filtration barrier, regulate glomerular permeability to albumin via their contractile properties. Both insulin- and high glucose (HG)-dependent activation of protein kinase G type Iα (PKGIα) cause reorganization of the actin cytoskeleton and podocyte disruption. Vasodilator-stimulated phosphoprotein (VASP) is a substrate for PKGIα and involved in the regulation of actin cytoskeleton dynamics. We investigated the role of the PKGIα/VASP pathway in the regulation of podocyte permeability to albumin. We evaluated changes in high insulin- and/or HG-induced transepithelial albumin flux in cultured rat podocyte monolayers. Expression of PKGIα and downstream proteins was confirmed by western blot and immunofluorescence. We demonstrate that insulin and HG induce changes in the podocyte contractile apparatus via PKGIα-dependent regulation of the VASP phosphorylation state, increase VASP colocalization with PKGIα, and alter the subcellular localization of these proteins in podocytes. Moreover, VASP was implicated in the insulin- and HG-dependent dynamic remodelling of the actin cytoskeleton and, consequently, increased podocyte permeability to albumin under hyperinsulinaemic and hyperglycaemic conditions. These results indicate that insulin- and HG-dependent regulation of albumin permeability is mediated by the PKGIα/VASP pathway in cultured rat podocytes. This molecular mechanism may explain podocytopathy and albuminuria in diabetes.

scholarly journals Rho Kinase‐mediated Regulation of Actin Cytoskeleton Dynamics Participates in NFATc3 Nuclear Transport

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Juan Manuel Ramiro‐Diaz ◽  
Carlos Hiroshi Nitta ◽  
Mingma Sherpa ◽  
Laura Veronica Gonzalez Bosc
Keyword(s):  
Actin Cytoskeleton ◽  
Nuclear Transport ◽  
Rho Kinase ◽  
Cytoskeleton Dynamics ◽  
Regulation Of Actin Cytoskeleton

p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton

2004 ◽  
Vol 286 (4) ◽  
pp. F693-F701 ◽  
Author(s):  
Louis C. Martineau ◽  
Lyne I. McVeigh ◽  
Bernard J. Jasmin ◽  
Chris R. J. Kennedy
Keyword(s):  
Actin Cytoskeleton ◽  
Map Kinase ◽  
Mechanical Stress ◽  
P38 Map Kinase ◽  
Receptor Expression ◽  
Prostaglandin E ◽  
Glomerular Permeability ◽  
Ep4 Receptor ◽  
Filtration Barrier ◽  
Cox 2

A dynamic cytoskeleton allows podocytes to withstand significant mechanical stress on elevation of intraglomerular capillary pressure (Pgc). However, vasoactive hormones, such as prostaglandin E2 (PGE2), may challenge the integrity of the actin cytoskeleton, alter podocyte morphology, and compromise glomerular permeability. PGE2 synthesis correlates with the onset of proteinuria and increased Pgc following reduced nephron mass. We investigated the interplay among mechanical stress, cyclooxygenase (COX), E-prostanoid (EP) receptor expression, and the actin cytoskeleton, using an in vitro model of cell stretch. Immortalized mouse podocytes grown on flexible silicone membranes were cyclically stretched (5% elongation, 0.5 Hz) for 2 h. EP4 and COX-2 mRNA increased three- and sevenfold above nonstretched controls, whereas EP1 and COX-1 levels were unchanged. Six hours of stretch resulted in a threefold increase in PGE2-stimulated cAMP accumulation, a measure of EP4 receptor function, and an increase in COX-2 protein. The stretch-induced effects on COX-2/EP4 expression and EP4-induced cAMP production were attributable to p38 MAP kinase, as blockade of this pathway, but not of ERK or JNK, abrogated the response. These stretch-induced changes in expression were transcriptionally dependent as they were actinomycin D sensitive. Finally, we investigated the influence of enhanced EP4 signaling on the actin cytoskeleton. Addition of PGE2 resulted in actin filament depolymerization observable only in stretched cells. Our results indicate that key components of the eicosanoid pathway are upregulated by mechanically stimulated p38 MAP kinase in podocytes. Enhanced EP4 receptor signaling may undermine podocyte cytoskeletal dynamics and thereby compromise filtration barrier function under conditions of increased Pgc.

scholarly journals Role of the p66Shc Isoform in Insulin-like Growth Factor I Receptor Signaling through MEK/Erk and Regulation of Actin Cytoskeleton in Rat Myoblasts

2004 ◽  
Vol 279 (42) ◽  
pp. 43900-43909 ◽  
Author(s):  
Annalisa Natalicchio ◽  
Luigi Laviola ◽  
Claudia De Tullio ◽  
Lucia Adelaide Renna ◽  
Carmela Montrone ◽  
...  
Keyword(s):  
Growth Factor ◽  
Actin Cytoskeleton ◽  
Insulin Like Growth Factor ◽  
Receptor Signaling ◽  
Factor I ◽  
Growth Factor I ◽  
Regulation Of Actin Cytoskeleton

scholarly journals An Emerging Role of PRRT2 in Regulating Growth Cone Morphology

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2666
Author(s):  
Elisa Savino ◽  
Fabrizia Guarnieri ◽  
Jin-Wu Tsai ◽  
Anna Corradi ◽  
Fabio Benfenati ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Growth Cone ◽  
Hippocampal Neurons ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Growth Cones ◽  
Cone Morphology ◽  
Infantile Seizures ◽  
Cytoskeleton Dynamics

Mutations in the PRRT2 gene are the main cause for a group of paroxysmal neurological diseases including paroxysmal kinesigenic dyskinesia, episodic ataxia, benign familial infantile seizures, and hemiplegic migraine. In the mature central nervous system, the protein has both a functional and a structural role at the synapse. Indeed, PRRT2 participates in the regulation of neurotransmitter release, as well as of actin cytoskeleton dynamics during synaptogenesis. Here, we show a role of the protein also during early stages of neuronal development. We found that PRRT2 accumulates at the growth cone in cultured hippocampal neurons. Overexpression of the protein causes an increase in the size and the morphological complexity of growth cones. In contrast, the growth cones of neurons derived from PRRT2 KO mice are smaller and less elaborated. Finally, we demonstrated that the aberrant shape of PRRT2 KO growth cones is associated with a selective alteration of the growth cone actin cytoskeleton. Our data support a key role of PRRT2 in the regulation of growth cone morphology during neuronal development.

scholarly journals Exploring the Possible Role of Lysine Acetylation onEntamoeba histolyticaVirulence: A Focus on the Dynamics of the Actin Cytoskeleton

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
L. López-Contreras ◽  
V. I. Hernández-Ramírez ◽  
A. E. Lagunes-Guillén ◽  
Sarita Montaño ◽  
B. Chávez-Munguía ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Effective Means ◽  
Cell Movement ◽  
Lysine Acetylation ◽  
Formation Processes ◽  
Severe Impairment ◽  
Cytoskeleton Remodeling ◽  
Cytoskeleton Dynamics

Cytoskeleton remodeling can be regulated, among other mechanisms, by lysine acetylation. The role of acetylation on cytoskeletal and other proteins ofEntamoeba histolyticahas been poorly studied. Dynamic rearrangements of the actin cytoskeleton are crucial for amebic motility and capping formation, processes that may be effective means of evading the host immune response. Here we report the possible effect of acetylation on the actin cytoskeleton dynamics andin vivovirulence ofE. histolytica. Using western blot, immunoprecipitation, microscopy assays, andin silicoanalysis, we show results that strongly suggest that the increase in Aspirin-induced cytoplasm proteins acetylation reduced cell movement and capping formation, likely as a consequence of alterations in the structuration of the actin cytoskeleton. Additionally, intrahepatic inoculation of Aspirin-treated trophozoites in hamsters resulted in severe impairment of the amebic virulence. Taken together, these results suggest an important role for lysine acetylation in amebic invasiveness and virulence.

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