Contractile proteins in podocytes: immunocytochemical localization of actin and alpha-actinin in normal and nephrotic rat kidneys

Lachapelle, Mario; Bendayan, Moı̈se

doi:10.1007/bf02899534

Cited by 41 publications

(30 citation statements)

References 19 publications

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“…Several reports have documented an abnormal distribution and disaggregation of podocyte actin microfilaments during the development of foot process effacement (30 -32). Concomitant redistribution of actin and ␣-actinin in the podocytes of nephrotic rats has also been reported (30,33), resulting in dysregulation of actin filament bundling in foot processes and finally yielding disruption of normal foot process function. Such alterations in cytoskeletal function might explain the characteristic changes to podocytes observed in FSGS.…”

Section: Discussionmentioning

confidence: 88%

Focal and Segmental Glomerulosclerosis in Mice with Podocyte-Specific Expression of Mutant α-Actinin-4

Michaud

Lemieux²,

Dubé

et al. 2003

Journal of the American Society of Nephrology

144

124

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Abstract. Mutations in the gene encoding ␣-actinin-4 (ACTN4), an actin crosslinking protein, are associated with a form of autosomal dominant focal segmental glomerulosclerosis (FSGS). To better study its progression, a transgenic mouse model was developed by expressing murine ␣-actinin-4 containing a mutation analogous to that affecting a human FSGS family in a podocyte-specific manner using the murine nephrin promoter. Consistent with human ACTN4-associated FSGS, which shows incomplete penetrance, a proportion of the transgenic mice exhibited significant albuminuria (8 of 18), while the overall average systolic BP was elevated in both proteinuric and non-proteinuric ACTN4-mutant mice. Immunofluorescence confirmed podocyte-specific expression of mutant ␣-actinin-4, and real-time RT-PCR revealed that HA-ACTN4 mRNA levels were higher in proteinuric versus non-proteinuric ACTN4-mutant mice. Only proteinuric mice exhibited histologic features consistent with human ACTN4-associated FSGS, including segmental sclerosis and tuft adhesion of some glomeruli, tubular dilatation, mesangial matrix expansion, as well as regions of podocyte vacuolization and foot process fusion. Consistent with such podocyte damage, proteinuric ACTN4-mutant kidneys exhibited significantly reduced mRNA and protein levels of the slit diaphragm component, nephrin. This newly developed mouse model of human ACTN4-associated FSGS suggests a cause-and-effect relationship between actin cytoskeleton dysregulation by mutant ␣-actinin-4 and the deterioration of the nephrin-supported slit diaphragm complex.

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Section: Discussionmentioning

confidence: 88%

Focal and Segmental Glomerulosclerosis in Mice with Podocyte-Specific Expression of Mutant α-Actinin-4

Michaud

Lemieux²,

Dubé

et al. 2003

Journal of the American Society of Nephrology

144

124

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“…17 Previous observation demonstrated a transient dysregulation of ␣-actinin in podocytes just before the development of foot process effacement 18 and a concomitant redistribution of ␣-actinin and actin associated with PAN-induced nephrosis. 41 In addition, ␣-actinin has been shown to bind ␤ 1 integrin subunit and strengthen the podocyte-GBM interaction, thereby stabilizing glomerular architecture. 42,43 Taken together, these observations lead us to speculate that ␣-actinin may mediate A 2A R agonist's effect on podocyte actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Activation of Adenosine 2A Receptors Preserves Structure and Function of Podocytes

Awad

Rouse

Liu

et al. 2008

Journal of the American Society of Nephrology

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Adenosine 2A receptor (A 2A R) activation was recently shown to be renoprotective in diabetic nephropathy. A 2A R are found in glomeruli and have been shown to associate with the podocyte cytoskeletal protein ␣-actinin-4, but the effect of their activation on podocyte structure and function is unknown. Podocyte injury was induced in C57BL/6 mice with puromycin aminonucleoside, and the selective A 2A R agonist ATL313 was found to attenuate the resulting albuminuria and foot process fusion. The selective A 2A R antagonist ZM241385 reversed the effects of ATL313. In vitro, A 2A R mRNA and protein were expressed in a conditionally immortalized podocyte cell line, and A 2A R-like immunoreactivity co-localized with the actin cytoskeleton. Treatment with ATL313 also blocked the increased podocyte permeability to albumin and disruption of the actin cytoskeleton that accompanied puromycin aminonucleosideinduced injury in vitro. ATL313 was ineffective, however, in the presence of the A 2A R antagonist and in A 2A R-deficient podocytes. It was concluded that A 2A R activation reduces glomerular proteinuria, at least in part, by preserving the normal structure of podocyte foot processes, slit diaphragms, and actin cytoskeleton.

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“…␣-Actinin-4 has been shown to be widely expressed in podocyte foot processes, colocalizing with actin stress fibers (245). Induction of proteinuria with puromycin in rats resulted in foot process retraction and progressive podocyte damage and was preceded by an increased ␣-actinin expression (429,435).…”

Section: G Actin-associated Molecules In Podocyte Damagementioning

confidence: 99%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,322

1,278

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Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

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Contractile proteins in podocytes: immunocytochemical localization of actin and alpha-actinin in normal and nephrotic rat kidneys

Cited by 41 publications

References 19 publications

Focal and Segmental Glomerulosclerosis in Mice with Podocyte-Specific Expression of Mutant α-Actinin-4

Focal and Segmental Glomerulosclerosis in Mice with Podocyte-Specific Expression of Mutant α-Actinin-4

Activation of Adenosine 2A Receptors Preserves Structure and Function of Podocytes

Cell Biology of the Glomerular Podocyte

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