Developmental Expression and Localization of Protein Phosphatase 2A in the Kidney † 1649

Heller, Felice

doi:10.1203/00006450-199704001-01668

Cited by 11 publications

(18 citation statements)

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“…In a recent study, expression of serine/threonine protein phosphatase 2A (PP2A) was found in developing podocytes of the newborn kidney in vivo but was absent from adult glomeruli (Everett et al 1999). While the latter study could not reveal the function of PP2A in devel-oping podocytes, we demonstrate here the role of protein serine/threonine phosphorylation by PP2A in the regulation of MT dynamics during podocyte process formation.…”

Section: Introductioncontrasting

confidence: 56%

Process formation of podocytes: morphogenetic activity of microtubules and regulation by protein serine/threonine phosphatase PP2A

Kobayashi

Reiser

Schwarz

et al. 2001

Histochem Cell Biol

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Podocytes possess major processes containing microtubules (MTs) and intermediate filaments and foot processes containing actin filaments (AFs) as core cytoskeletal elements. Although the importance of these cytoskeletal elements for maintaining podocyte processes was previously shown, so far no data are available concerning the developmental regulation of podocyte process formation. A conditionally immortalized mouse podocyte cell line, which can be induced to develop processes similar to those found in vivo, was treated with various reagents to disrupt cytoskeletal elements or to inhibit protein phosphatases. MTs colocalized with vimentin intermediate filaments but not with AFs. After AF disassembly, major processes were maintained, whereas after depolymerization of MTs, podocytes lost their processes, rounded up, and maintained only actin-based peripheral projections. Suppression of MT elongation by nanomolar vinblastine or inhibition of serine/threonine phosphatase PP2A with okadaic acid abolished process formation. PP2A was expressed in undifferentiated but not in differentiated podocytes. One-and two-dimensional western blot analyses revealed a dose-dependent increase in serine/threonine phosphorylation after ok-adaic acid treatment. Hence, morphogenetic activity of MTs induces podocyte process formation via serine/threonine protein dephosphorylation by PP2A. These results may open new avenues for understanding the signaling mechanism underlying podocyte cytoskeleton alterations during development and in glomerular diseases.

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Section: Introductioncontrasting

confidence: 56%

Process formation of podocytes: morphogenetic activity of microtubules and regulation by protein serine/threonine phosphatase PP2A

Kobayashi

Reiser

Schwarz

et al. 2001

Histochem Cell Biol

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“…We also found that PP2A B56a expression in BBMs was greatest in the most immature rats and decreased with age, regardless of strain (WKY and SHR). PP2A activity and the expression of A structural, C catalytic and B55 regulatory subunits of PP2A have also been reported to be developmentally regulated, with highest expression in the fetal kidney (26).…”

Section: Discussionmentioning

confidence: 98%

Protein Phosphatase 2A B56α During Development in the Spontaneously Hypertensive Rat

Yang

Yu²,

Asico³

et al. 2004

Clinical and Experimental Hypertension

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Mistargeting of the regulatory subunit of protein phosphatase 2A (PP2A), B56alpha is involved in the hyperphosphorylation and desensitization of the D1 dopamine receptor in renal proximal tubules of spontaneously hypertensive rats (SHRs). However, the renal expression of B56alpha before hypertension develops is not known. Therefore, we studied the expression of B56alpha and PP2A activity in the kidney during development in the SHR and its normotensive control, the Wistar-Kyoto (WKY) rat. PP2A B56alpha was expressed in proximal and distal tubules with no differences in the pattern of expression in WKY and SHRs at any age. In brush border membranes of renal proximal tubules, PP2A B56alpha protein was greatest in the immature rats and decreased with development. However, PP2A activity did not change with age. PP2A B56alpha protein and PP2A activity were similar in WKY and SHRs except at 2 weeks when both PP2A B56alpha protein and PP2A activity were higher in SHRs than in WKY rats. The PP2A catalytic subunit co-immunoprecipitated with the D1 receptor in renal proximal tubule cells. It is possible that the increased expression of PP2A B56alpha and increased basal PP2A activity in the young, especially in the SHRs, may serve as a compensatory mechanism in the increased phosphorylation and decreased renal D1 receptor function, including D1-receptor mediated stimulation in renal proximal tubules of SHRs.

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“…[20] Phylogenetic relationship shows that with similar expression values there is an evolutionary relation shown by the phylogenetic tree. [4]…”

Section: Discussionmentioning

confidence: 99%

Cluster analysis and phylogenetic relationship in biomarker identification of type 2 diabetes and nephropathy

Guttula¹,

Rao²,

Sridhar³

et al. 2010

Int J Diab Dev Ctries

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Cluster analysis of DNA microarray data that uses statistical algorithms to arrange the genes according to similarity in patterns of gene expression and the output displayed graphically is described in this article. Hierarchical clustering is a multivariate tool often used in phylogenetics, comparative genomics to relate the evolution of species. The patterns seen in microarray expression data can be interpreted as indications of the status of the genes responsible for nephropathy in peripheral blow cells of type 2 diabetes (T2DN). Out of 415 genes totally expressed in the 3 DNA chips it was concluded that only 116 genes expressed in T2DN and in that only 50 are functional genes. These 50 functional genes are responsible for diabetic nephropathy; of these 50, some of the genes which are more expressed and responsible are AGXT: Alanine-glyoxylate aminotransferase, RHOD: Ras homolog gene family, CAPN6: Calpain 6, EFNB2: Ephrin-B2, ANXA7: Annexin A7, PEG10: Paternally expressed 10, DPP4: Dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2), ENSA: Endosulfine alpha, IGFBP2: Insulin-like growth factor binding protein 2, 36kDa, CENPB: Centromere protein B, 80kDa, MLL3: Myeloid/lymphoid or mixed-lineage leukemia 3, BDNF: Brain-derived neurotrophic factor, EIF4A2: Eukaryotic translation initiation factor 4A, isoform 2, PPP2R1A: Protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform. Fifty genes and their nucleotide sequences are taken from NCBI and a phylogenetic tree is constructed using CLUSTAL W and the distances are closer to each other concluding that based on the sequence similarity and evolution the genes are expressed similarly. Literature survey is done for each gene in OMIM and the genes responsible for diabetic nephropathy are listed.

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Developmental Expression and Localization of Protein Phosphatase 2A in the Kidney † 1649

Cited by 11 publications

References 0 publications

Process formation of podocytes: morphogenetic activity of microtubules and regulation by protein serine/threonine phosphatase PP2A

Process formation of podocytes: morphogenetic activity of microtubules and regulation by protein serine/threonine phosphatase PP2A

Protein Phosphatase 2A B56α During Development in the Spontaneously Hypertensive Rat

Cluster analysis and phylogenetic relationship in biomarker identification of type 2 diabetes and nephropathy

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