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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
Department: Division of the Deputy Vice-Chancellor and Vice-President (Research)
Statement of
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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