Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/83397
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Type: Journal article
Title: Chaperone-assisted selective autophagy is essential for muscle maintenance
Author: Arndt, V.
Dick, N.
Tawo, R.
Dreiseidler, M.
Wenzel, D.
Hesse, M.
Furst, D.
Saftig, P.
Saint, R.
Fleischmann, B.
Hoch, M.
Hohfeld, J.
Citation: Current Biology, 2010; 20(2):143-148
Publisher: Dell Press
Issue Date: 2010
ISSN: 0960-9822
1879-0445
Department: Division of the Deputy Vice-Chancellor and Vice-President (Research)
Statement of
Responsibility: 
Verena Arndt, Nikolaus Dick, Riga Tawo, Michael Dreiseidler, Daniela Wenzel, Michael Hesse, Dieter O. Fürst, Paul Saftig, Robert Saint, Bernd K. Fleischmann, Michael Hoch, and Jörg Höhfeld
Abstract: How are biological structures maintained in a cellular environment that constantly threatens protein integrity? Here we elucidate proteostasis mechanisms affecting the Z disk, a protein assembly essential for actin anchoring in striated muscles, which is subjected to mechanical, thermal, and oxidative stress during contraction [1]. Based on the characterization of the Drosophila melanogaster cochaperone Starvin (Stv), we define a conserved chaperone machinery required for Z disk maintenance. Instead of keeping Z disk proteins in a folded conformation, this machinery facilitates the degradation of damaged components, such as filamin, through chaperone-assisted selective autophagy (CASA). Stv and its mammalian ortholog BAG-3 coordinate the activity of Hsc70 and the small heat shock protein HspB8 during disposal that is initiated by the chaperone-associated ubiquitin ligase CHIP and the autophagic ubiquitin adaptor p62. CASA is thus distinct from chaperone-mediated autophagy, previously shown to facilitate the ubiquitin-independent, direct translocation of a client across the lysosomal membrane [2]. Impaired CASA results in Z disk disintegration and progressive muscle weakness in flies, mice, and men. Our findings reveal the importance of chaperone-assisted degradation for the preservation of cellular structures and identify muscle as a tissue that highly relies on an intact proteostasis network, thereby shedding light on diverse myopathies and aging.
Keywords: Proteins; Cellbio; Humdisease
Rights: ©2010 Elsevier Ltd All rights reserved
RMID: 0020134421
DOI: 10.1016/j.cub.2009.11.022
Appears in Collections:Genetics publications

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