MAGI-2 and scaffold proteins in glomerulopathy

Empitu, Maulana A.; Kadariswantiningsih, Ika N.; Aizawa, Masashi; Asanuma, Katsuhiko

doi:10.1152/ajprenal.00292.2018

Cited by 14 publications

(20 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26,27 As the previous studies showed, the function of MAGI-2 for the SDs remains obscure. 28 Our study has revealed that MAGI-2 orchestrates the localization of Nephrin and Neph1 through PDZ domains together with other scaffold proteins (Figure 8). In other words, MAGI-2 plays a critical role in stabilizing the glomerular filtration barrier as a scaffold protein.…”

Section: Discussionmentioning

confidence: 81%

“…Membrane-associated guanylate kinase inverted 2 (MAGI-2) is also one of the scaffold proteins identified in neuronal spines and podocytes. [26][27][28] It is already been established that MAGI-2 mediates the signaling of G protein-coupled receptors, RhoA, and Ras-associated protein-1. [29][30][31] Previously, we reported that podocyte-specific MAGI-2 knockout (KO) mice exhibit glomerulosclerosis and kidney failure in a manner similar to FSGS.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

Yamada

Shirata

Makino

et al. 2021

Kidney International

Self Cite

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

Yamada

Shirata

Makino

et al. 2021

Kidney International

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, no previous studies have found associations between APOBEC3 and AD. MAGI2 regulates apoptosis, cytoskeletal reorganization, and glomerular development and is broadly expressed in the brain, thyroid, and 16 other tissues, including blood [32]. MAGI2 is a candidate gene associated with multiple phenotypes, as demonstrated by Alzheimer's Disease Neuroimaging Initiative genetic studies [33].…”

Section: Discussionmentioning

confidence: 99%

Identifying Blood Transcriptome Biomarkers of Alzheimer’s Disease Using Transgenic Mice

et al. 2020

View full text Add to dashboard Cite

The testing of pathological biomarkers of Alzheimer’s disease (AD), such as amyloid beta and tau, is time-consuming, expensive, and invasive. Here, we used 3xTg-AD mice to identify and validate putative novel blood transcriptome biomarkers of AD that can potentially be identified in the blood of patients. mRNA was extracted from the blood and hippocampus of 3xTg-AD and control mice at different ages and used for microarray analysis. Network and functional analyses revealed that the differentially expressed genes between AD and control mice modulated the immune and neuroinflammation systems. Five novel gene transcripts (Cdkn2a, Apobec3, Magi2, Parp3, and Cass4) showed significant increases with age, and their expression in the blood was collated with that in the hippocampus only in AD mice. We further assessed previously identified candidate biomarker genes. The expression of Trem1 and Trem2 in both the blood and brain was significantly increased with age. Decreased Tomm40 and increased Pink1 mRNA levels were observed in the mouse blood. The changes in the expression of Snca and Apoe mRNA in the mouse blood and brain were similar to those found in human AD blood. Our results demonstrated that the immune and neuroinflammatory system is involved in the pathophysiologies of aging and AD and that the blood transcriptome might be useful as a biomarker of AD.

show abstract

“…Because MAGI2 binds b-catenin at adherence junctions, 43,44 it has been suggested that MAGI2 could modulate Wnt/b-catenin signaling. 45 Pharmacological activation of b-catenin induced albuminuria in wild-type mice but not in b-catenin-KO littermates. 46 As shown in Con8 rat mammary epithelial tumor cells, dexamethasone prevents b-catenin phosphorylation and recruits it from the nucleus to adherence junctions.…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

Jobst-Schwan

Hoogstraten

Kolvenbach

et al. 2019

Kidney International

View full text Add to dashboard Cite

Recently, recessive mutations of MAGI2 were identified as a cause of steroid-resistant nephrotic syndrome (SRNS) in humans and mice. To further delineate the pathogenesis of MAGI2 loss of function, we generated stable knockout lines for the two zebrafish orthologues magi2a and magi2b by CRISPR/Cas9. We also developed a novel assay for the direct detection of proteinuria in zebrafish independent of transgenic background. Whereas knockout of magi2b did not yield a nephrotic syndrome phenotype, magi2a -/larvae developed ascites, periorbital edema, and proteinuria, as indicated by increased excretion of low molecular weight protein. Electron microscopy demonstrated extensive podocyte foot process effacement. As in human SRNS, we observed genotype/phenotype correlation, with edema onset occurring earlier in zebrafish with truncating alleles (5-6 days post fertilization) versus hypomorphic alleles (19-20 days post fertilization). Paradoxically, corticosteroid treatment exacerbated the phenotype, with earlier onset of edema. In contrast, treatment with cyclosporine A or tacrolimus had no significant effect. Although RhoA signaling has been implicated as a downstream mediator of MAGI2 activity, targeting of the RhoA pathway did not modify the nephrotic syndrome phenotype. In the first CRISPR/Cas9 zebrafish knockout model of SRNS, we found that corticosteroids may have a paradoxical effect in the setting of specific genetic mutations.

show abstract

MAGI-2 and scaffold proteins in glomerulopathy

Cited by 14 publications

References 99 publications

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

Identifying Blood Transcriptome Biomarkers of Alzheimer’s Disease Using Transgenic Mice

Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

Contact Info

Product

Resources

About