Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0083133
Title: Wtip- and Gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier
Authors: Xiao Z.
Rodriguez P.Q.
He L.
Betsholtz C.
Tryggvason K. 
Patrakka J.
Keywords: binding protein
dendrin
growth arrest and DNA damage inducible protein 45 alpha
transcription factor
unclassified drug
Wt1 interacting protein
adult
animal experiment
animal model
animal tissue
article
cell nucleus
controlled study
embryo
genetic transcription
glomerular filtration barrier
human
human cell
injury severity
kidney development
kidney injury
mouse
nonhuman
podocyte
protein function
protein protein interaction
protein transport
proteinuria
Animals
Carrier Proteins
Cell Cycle Proteins
Cell Nucleus
Female
Gene Expression Regulation, Developmental
Glomerular Filtration Rate
Kidney Glomerulus
Male
Mice
Mice, Knockout
Morphogenesis
Nerve Tissue Proteins
Nuclear Proteins
Podocytes
Protein Binding
Protein Transport
Issue Date: 2013
Citation: Xiao Z., Rodriguez P.Q., He L., Betsholtz C., Tryggvason K., Patrakka J. (2013). Wtip- and Gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier. PLoS ONE 8 (12) : e83133. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0083133
Rights: Attribution 4.0 International
Abstract: Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. Especially, the highly specialized cell-cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. This is highlighted by the fact that mutations in molecular components of the slit diaphragm, including nephrin and Cd2-associated protein (Cd2ap), result in proteinuric diseases in man. Dendrin is a poorly characterized cytosolic component of the slit diaphragm in where it interacts with nephrin and Cd2ap. Dendrin is highly specific for the podocyte slit diaphragm, suggesting that it has a dedicated role in the glomerular filtration barrier. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile, and had a normal life span. Morphologically, the glomerulogenesis proceeded normally and adult dendrin-deficient mice showed normal glomerular histology. No significant proteinuria was observed. Following glomerular injury, lack of dendrin did not affect the severity of the damage or the recovery process. Yeast two-hybrid screen and co-immunoprecipitation experiments showed that dendrin binds to Wt1-interacting protein (Wtip) and growth arrest and DNA-damage-inducible 45 alpha (Gadd45a). Wtip and Gadd45a mediate gene transcription in the nucleus, suggesting that dendrin may have similar functions in podocytes. In line with this, we observed the relocation of dendrin to nucleus in adriamycin nephropathy model. Our results indicate that dendrin is dispensable for the function of the normal glomerular filtration barrier and that dendrin interacts with Wtip and Gadd45a. © 2013 Xiao et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161440
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0083133
Rights: Attribution 4.0 International
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