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Vol. 18, Issue 12, 4803-4812, December 2007

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Role of Hsp104 in the Propagation and Inheritance of the [Het-s] Prion

Laboratoire de Génétique Moléculaire des Champignons, Institut de Biochimie et de Génétique Cellulaires, Unité Mixte de Recherche 5095 Centre National de la Recherche Scientifique/Université de Bordeaux 2, 33077 Bordeaux Cedex, France

Submitted July 11, 2007; Revised September 5, 2007; Accepted September 10, 2007
Monitoring Editor: Jonathan Weissman

The chaperones of the ClpB/HSP100 family play a central role in thermotolerance in bacteria, plants, and fungi by ensuring solubilization of heat-induced protein aggregates. In addition in yeast, Hsp104 was found to be required for prion propagation. Herein, we analyze the role of Podospora anserina Hsp104 (PaHsp104) in the formation and propagation of the [Het-s] prion. We show that PaHsp104 strains propagate [Het-s], making [Het-s] the first native fungal prion to be propagated in the absence of Hsp104. Nevertheless, we found that [Het-s]-propagon numbers, propagation rate, and spontaneous emergence are reduced in a PaHsp104 background. In addition, inactivation of PaHsp104 leads to severe meiotic instability of [Het-s] and abolishes its meiotic drive activity. Finally, we show that PaHSP104 strains are less susceptible than wild type to infection by exogenous recombinant HET-s(218–289) prion amyloids. Like [URE3] and [PIN⁺] in yeast but unlike [PSI⁺], [Het-s] is not cured by constitutive PaHsp104 overexpression. The observed effects of PaHsp104 inactivation are consistent with the described role of Hsp104 in prion aggregate shearing in yeast. However, Hsp104-dependency appears less stringent in P. anserina than in yeast; presumably because in Podospora prion propagation occurs in a syncitium.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Sven J. Saupe (sven.saupe{at}ibgc.u-bordeaux2.fr).