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Exp Mol Med. 2018 Jun 28;50(6):75. doi: 10.1038/s12276-018-0108-z.

Targeted deletion of the AAA-ATPase Ruvbl1 in mice disrupts ciliary integrity and causes renal disease and hydrocephalus.

Author information

1
Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
2
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
3
Department of Pediatrics, University Hospital of Cologne, Cologne, Germany.
4
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
5
Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
6
Department of Radiology, University Hospital of Cologne, Cologne, Germany.
7
Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Cologne, Germany.
8
Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.
9
Department of Pathology, University Hospital of Cologne, Cologne, Germany.
10
Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany.
11
Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
12
Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Cologne, Germany.
13
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
14
Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany. Bernhard.schermer@uk-koeln.de.
15
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. Bernhard.schermer@uk-koeln.de.
16
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. Bernhard.schermer@uk-koeln.de.
17
Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Cologne, Germany. Bernhard.schermer@uk-koeln.de.

Abstract

Ciliopathies comprise a large number of hereditary human diseases and syndromes caused by mutations resulting in dysfunction of either primary or motile cilia. Both types of cilia share a similar architecture. While primary cilia are present on most cell types, expression of motile cilia is limited to specialized tissues utilizing ciliary motility. We characterized protein complexes of ciliopathy proteins and identified the conserved AAA-ATPase Ruvbl1 as a common novel component. Here, we demonstrate that Ruvbl1 is crucial for the development and maintenance of renal tubular epithelium in mice: both constitutive and inducible deletion in tubular epithelial cells result in renal failure with tubular dilatations and fewer ciliated cells. Moreover, inducible deletion of Ruvbl1 in cells carrying motile cilia results in hydrocephalus, suggesting functional relevance in both primary and motile cilia. Cilia of Ruvbl1-negative cells lack crucial proteins, consistent with the concept of Ruvbl1-dependent cytoplasmic pre-assembly of ciliary protein complexes.

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