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@ARTICLE{Sachs:614226,
author = {Sachs, Wiebke and Blume, Lukas and Loreth, Desiree and
Schebsdat, Lisa and Hatje, Favian and Koehler, Sybille and
Wedekind, Uta and Sachs, Marlies and Zieliniski, Stephanie
and Brand, Johannes and Conze, Christian and Florea, Bogdan
I. and Heppner, Frank and Krüger, Elke and Rinschen, Markus
M. and Kretz, Oliver and Thünauer, Roland and
Meyer-Schwesinger, Catherine},
title = {{T}he proteasome modulates endocytosis specifically in
glomerular cells to promote kidney filtration},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {PUBDB-2024-05766},
pages = {1897},
year = {2024},
note = {DFG Research Infrastructure Portal: $RI_00489$ for
excellent technical assistance},
abstract = {Kidney filtration is ensured by the interaction of
podocytes, endothelial and mesangial cells. Immunoglobulin
accumulation at the filtration barrier is pathognomonic for
glomerular injury. The mechanisms that regulate filter
permeability are unknown. Here, we identify a pivotal role
for the proteasome in a specific cell type. Combining
genetic and inhibitor-based human, pig, mouse, and
Drosophila models we demonstrate that the proteasome
maintains filtration barrier integrity, with podocytes
requiring the constitutive and glomerular endothelial cells
the immunoproteasomal activity. Endothelial immunoproteasome
deficiency as well as proteasome inhibition disrupt the
filtration barrier in mice, resulting in pathologic
immunoglobulin deposition. Mechanistically, we observe
reduced endocytic activity, which leads to altered membrane
recycling and endocytic receptor turnover. This work expands
the concept of the (immuno)proteasome as a control protease
orchestrating protein degradation and antigen presentation
and endocytosis, providing new therapeutic targets to treat
disease-associated glomerular protein accumulations.},
cin = {CSSB-CF-ALFM},
ddc = {500},
cid = {I:(DE-H253)CSSB-CF-ALFM-20210629},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-H253)ALFM-20250101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38429282},
UT = {WOS:001447479900019},
doi = {10.1038/s41467-024-46273-0},
url = {https://bib-pubdb1.desy.de/record/614226},
}