Universität zu Köln

Kustermann, Monika, Manta, Linda, Paone, Christoph, Kustermann, Jochen, Lausser, Ludwig, Wiesner, Cora, Eichinger, Ludwig ORCID: 0000-0003-1594-6117, Clemen, Christoph S., Schroeder, Rolf, Kestler, Hans A., Sandri, Marco, Rottbauer, Wolfgang and Just, Steffen (2018). Loss of the novel Vcp (valosin containing protein) interactor Washc4 interferes with autophagy-mediated proteostasis in striated muscle and leads to myopathy in vivo. Autophagy, 14 (11). S. 1911 - 1928. PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 1554-8635

Full text not available from this repository.

Abstract

VCP/p97 (valosin containing protein) is a key regulator of cellular proteostasis. It orchestrates protein turnover and quality control in vivo, processes fundamental for proper cell function. In humans, mutations in VCP lead to severe myo- and neuro-degenerative disorders such as inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD), amyotrophic lateral sclerosis (ALS) or and hereditary spastic paraplegia (HSP). We analyzed here the in vivo role of Vcp and its novel interactor Washc4/Swip (WASH complex subunit 4) in the vertebrate model zebrafish (Danio rerio). We found that targeted inactivation of either Vcp or Washc4, led to progressive impairment of cardiac and skeletal muscle function, structure and cytoarchitecture without interfering with the differentiation of both organ systems. Notably, loss of Vcp resulted in compromised protein degradation via the proteasome and the macroautophagy/autophagy machinery, whereas Washc4 deficiency did not affect the function of the ubiquitin-proteasome system (UPS) but caused ER stress and interfered with autophagy function in vivo. In summary, our findings provide novel insights into the in vivo functions of Vcp and its novel interactor Washc4 and their particular and distinct roles during proteostasis in striated muscle cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kustermann, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Manta, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Paone, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Kustermann, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Lausser, Ludwig UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Cora UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichinger, Ludwig UNSPECIFIED orcid.org/0000-0003-1594-6117 UNSPECIFIED Clemen, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kestler, Hans A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sandri, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Rottbauer, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Just, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-201971
DOI:	10.1080/15548627.2018.1491491
Journal or Publication Title:	Autophagy
Volume:	14
Number:	11
Page Range:	S. 1911 - 1928
Date:	2018
Publisher:	TAYLOR & FRANCIS INC
Place of Publication:	PHILADELPHIA
ISSN:	1554-8635
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOPLASMIC-RETICULUM; PROTEASOME SYSTEM; VCP/P97; ZEBRAFISH; DISEASE; COMPLEX; P97; DEGENERATION; DEGRADATION; EXPRESSION Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20197