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Molecular and Cellular Biology, July 2009, p. 3738-3745, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.00201-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Yeast AAA+ Chaperone Hsp104 Is Part of a Network That Links the Actin Cytoskeleton with the Inheritance of Damaged Proteins{triangledown}

Peter Tessarz,1,{dagger} Michael Schwarz,2 Axel Mogk,1 and Bernd Bukau1*

Universität Heidelberg, Zentrum fuer Molekulare Biologie Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany,1 Max Planck Institute of Biochemistry, Department of Molecular Cell Biology, Am Klopferspitz 18, 82152 Martinsried/Munich, Germany2

Received 13 February 2009/ Returned for modification 6 April 2009/ Accepted 15 April 2009

The yeast AAA+ chaperone Hsp104 is essential for the development of thermotolerance and for the inheritance of prions. Recently, Hsp104, together with the actin cytoskeleton, has been implicated in the asymmetric distribution of carbonylated proteins. Here, we investigated the interplay between Hsp104 and actin by using a dominant-negative variant of Hsp104 (HAP/ClpP) that degrades substrate proteins instead of remodeling them. Coexpression of HAP/ClpP causes defects in morphology and the actin cytoskeleton. Taking a candidate approach, we identified Spa2, a member of the polarisome complex, as an Hsp104 substrate. Furthermore, we provided genetic evidence that links Spa2 and Hsp104 to Hof1, a member of the cytokinesis machinery. Spa2 and Hof1 knockout cells are affected in the asymmetric distribution of damaged proteins, suggesting that Hsp104, Spa2, and Hof1 are members of a network controlling the inheritance of carbonylated proteins.


* Corresponding author. Mailing address: Universität Heidelberg, Zentrum fuer Molekulare Biologie Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany. Phone: 49-6221-54-6795. Fax: 49-6221-54-5894. E-mail: bukau{at}zmbh.uni-heidelberg.de

{triangledown} Published ahead of print on 27 April 2009.

{dagger} Present address: Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom.


Molecular and Cellular Biology, July 2009, p. 3738-3745, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.00201-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.