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The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration

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The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration. / Sachs, Wiebke; Blume, Lukas; Loreth, Desiree; Schebsdat, Lisa; Hatje, Favian; Koehler, Sybille; Wedekind, Uta; Sachs, Marlies; Zieliniski, Stephanie; Brand, Johannes; Conze, Christian; Florea, Bogdan I; Heppner, Frank; Krüger, Elke; Rinschen, Markus M; Kretz, Oliver; Thünauer, Roland; Meyer-Schwesinger, Catherine.

In: NAT COMMUN, Vol. 15, No. 1, 01.03.2024, p. 1897.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sachs, W, Blume, L, Loreth, D, Schebsdat, L, Hatje, F, Koehler, S, Wedekind, U, Sachs, M, Zieliniski, S, Brand, J, Conze, C, Florea, BI, Heppner, F, Krüger, E, Rinschen, MM, Kretz, O, Thünauer, R & Meyer-Schwesinger, C 2024, 'The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration', NAT COMMUN, vol. 15, no. 1, pp. 1897. https://doi.org/10.1038/s41467-024-46273-0

APA

Sachs, W., Blume, L., Loreth, D., Schebsdat, L., Hatje, F., Koehler, S., Wedekind, U., Sachs, M., Zieliniski, S., Brand, J., Conze, C., Florea, B. I., Heppner, F., Krüger, E., Rinschen, M. M., Kretz, O., Thünauer, R., & Meyer-Schwesinger, C. (2024). The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration. NAT COMMUN, 15(1), 1897. https://doi.org/10.1038/s41467-024-46273-0

Vancouver

Sachs W, Blume L, Loreth D, Schebsdat L, Hatje F, Koehler S et al. The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration. NAT COMMUN. 2024 Mar 1;15(1):1897. https://doi.org/10.1038/s41467-024-46273-0

Bibtex

@article{62c3fac22a234627b3b92722fa4d19a3,
title = "The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration",
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.",
keywords = "Mice, Humans, Animals, Swine, Proteasome Endopeptidase Complex, Endothelial Cells, Kidney Glomerulus/pathology, Kidney Diseases/pathology, Endocytosis, Immunoglobulins",
author = "Wiebke Sachs and Lukas Blume and Desiree Loreth and Lisa Schebsdat and Favian Hatje and Sybille Koehler and Uta Wedekind and Marlies Sachs and Stephanie Zieliniski and Johannes Brand and Christian Conze and Florea, {Bogdan I} and Frank Heppner and Elke Kr{\"u}ger and Rinschen, {Markus M} and Oliver Kretz and Roland Th{\"u}nauer and Catherine Meyer-Schwesinger",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = mar,
day = "1",
doi = "10.1038/s41467-024-46273-0",
language = "English",
volume = "15",
pages = "1897",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration

AU - Sachs, Wiebke

AU - Blume, Lukas

AU - Loreth, Desiree

AU - Schebsdat, Lisa

AU - Hatje, Favian

AU - Koehler, Sybille

AU - Wedekind, Uta

AU - Sachs, Marlies

AU - Zieliniski, Stephanie

AU - Brand, Johannes

AU - Conze, Christian

AU - Florea, Bogdan I

AU - Heppner, Frank

AU - Krüger, Elke

AU - Rinschen, Markus M

AU - Kretz, Oliver

AU - Thünauer, Roland

AU - Meyer-Schwesinger, Catherine

N1 - © 2024. The Author(s).

PY - 2024/3/1

Y1 - 2024/3/1

N2 - 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.

AB - 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.

KW - Mice

KW - Humans

KW - Animals

KW - Swine

KW - Proteasome Endopeptidase Complex

KW - Endothelial Cells

KW - Kidney Glomerulus/pathology

KW - Kidney Diseases/pathology

KW - Endocytosis

KW - Immunoglobulins

U2 - 10.1038/s41467-024-46273-0

DO - 10.1038/s41467-024-46273-0

M3 - SCORING: Journal article

C2 - 38429282

VL - 15

SP - 1897

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -