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Molecular heterogeneity of the dystrophin-associated protein complex in the mouse kidney nephron: differential alterations in the absence of utrophin and dystrophin


Haenggi, Tatjana; Schaub, Marcus C; Fritschy, Jean-Marc (2005). Molecular heterogeneity of the dystrophin-associated protein complex in the mouse kidney nephron: differential alterations in the absence of utrophin and dystrophin. Cell and Tissue Research, 319(2):299-313.

Abstract

The dystrophin-associated protein complex (DPC) consisting of syntrophin, dystrobrevin, and dystroglycan isoforms is associated either with dystrophin or its homolog utrophin. It is present not only in muscle cells, but also in numerous tissues, including kidney, liver, and brain. Using high-resolution immunofluorescence imaging and Western blotting, we have investigated the effects of utrophin and dystrophin gene deletion on the formation and membrane anchoring of the DPC in kidney epithelial cells, which co-express utrophin and low levels of the C-terminal dystrophin isoform Dp71. We show that multiple, molecularly distinct DPCs co-exist in the nephron; these DPCs have a segment-specific distribution and are only partially associated with utrophin in the basal membrane of tubular epithelial cells. In utrophin-deficient mice, a selective reduction of β2-syntrophin has been observed in medullary tubular segments, whereas α1-syntrophin and β1-syntrophin are retained, concomintant with an upregulation of β-dystroglycan, β-dystrobrevin, and Dp71. These findings suggest that β2-syntrophin is dependent on utrophin for association with the DPC, and that loss of utrophin is partially compensated by Dp71, allowing the preservation of the DPC in kidney epithelial cells. This hypothesis is confirmed by the almost complete loss of all DPC proteins examined in mice lacking full-length utrophin and all C-terminal dystrophin isoforms (utrophin0/0/mdx3Cv). The DPC thus critically depends on these proteins for assembly and/or membrane localization in kidney epithelial cells

Abstract

The dystrophin-associated protein complex (DPC) consisting of syntrophin, dystrobrevin, and dystroglycan isoforms is associated either with dystrophin or its homolog utrophin. It is present not only in muscle cells, but also in numerous tissues, including kidney, liver, and brain. Using high-resolution immunofluorescence imaging and Western blotting, we have investigated the effects of utrophin and dystrophin gene deletion on the formation and membrane anchoring of the DPC in kidney epithelial cells, which co-express utrophin and low levels of the C-terminal dystrophin isoform Dp71. We show that multiple, molecularly distinct DPCs co-exist in the nephron; these DPCs have a segment-specific distribution and are only partially associated with utrophin in the basal membrane of tubular epithelial cells. In utrophin-deficient mice, a selective reduction of β2-syntrophin has been observed in medullary tubular segments, whereas α1-syntrophin and β1-syntrophin are retained, concomintant with an upregulation of β-dystroglycan, β-dystrobrevin, and Dp71. These findings suggest that β2-syntrophin is dependent on utrophin for association with the DPC, and that loss of utrophin is partially compensated by Dp71, allowing the preservation of the DPC in kidney epithelial cells. This hypothesis is confirmed by the almost complete loss of all DPC proteins examined in mice lacking full-length utrophin and all C-terminal dystrophin isoforms (utrophin0/0/mdx3Cv). The DPC thus critically depends on these proteins for assembly and/or membrane localization in kidney epithelial cells

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Pathology and Forensic Medicine
Health Sciences > Histology
Life Sciences > Cell Biology
Language:English
Date:1 February 2005
Deposited On:04 Jul 2019 11:15
Last Modified:31 Jul 2020 02:50
Publisher:Springer
ISSN:0302-766X
OA Status:Green
Publisher DOI:https://doi.org/10.1007/s00441-004-0999-y
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicencespringer101007s004410040999y (Library Catalogue)
PubMed ID:15565469

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