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J. Biol. Chem., Vol. 279, Issue 12, 11489-11494, March 19, 2004

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Developmental Cell Death in Dictyostelium Does Not Require Paracaspase^*

Céline Roisin-Bouffay¶||, Marie-Françoise Luciani, Gérard Klein**, Jean-Pierre Levraud, Myriam Adam||, and Pierre Golstein

From the Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Universite de la Méditerranie, Parc Scientifique de Luminy, Case 906, 13288 Marseille Cedex 9, France, the ^**Laboratoire de Biochimie et Biophysique des Systèmes Intégrés, Commissariat à l'Energie Atomique-Grenoble, 38054 Grenoble Cedex 9, France, and the Unité Postulante Macrophages et Développement de l'Immunité, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France

Apoptotic cell death often requires caspases. Caspases are part of a family of related molecules including also paracaspases and metacaspases. Are molecules of this family generally involved in cell death? More specifically, do non-apoptotic caspase-independent types of cell death require paracaspases or metacaspases? Dictyostelium discoideum lends itself well to answering these questions because 1) it undergoes non-apoptotic developmental cell death of a vacuolar autophagic type and 2) it bears neither caspase nor metacaspase genes and apparently only one paracaspase gene. This only paracaspase gene can be inactivated by homologous recombination. Paracaspase-null clones were thus obtained in each of four distinct Dictyostelium strains. These clones were tested in two systems, developmental stalk cell death in vivo and vacuolar autophagic cell death in a monolayer system mimicking developmental cell death. Compared with parent cells, all of the paracaspase-null cells showed unaltered cell death in both test systems. In addition, paracaspase inactivation led to no alteration in development or interaction with a range of bacteria. Thus, in Dictyostelium, vacuolar programmed cell death in development and in a monolayer model in vitro would seem not to require paracaspase. To our knowledge, this is the first instance of developmental programmed cell death shown to be independent of any caspase, paracaspase or metacaspase. These results have implications as to the relationship in evolution between cell death and the caspase family.

Received for publication, November 21, 2003

^* This work was supported by INSERM, CNRS, MRT (ACI Biologie du Développement et Physiologie Intégrative), and ARC. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

^¶ Supported by Fondation pour la Recherche Médicale.

^|| Supported by EC Vth Framework Grant QLG1-CT1999-00739.

To whom correspondence should be addressed: Centre d'Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, 13288 Marseille Cedex 9, France. Tel.: 33-4-91-26-94-68; Fax: 33-4-91-26-94-30; E-mail: golstein{at}ciml.univ-mrs.fr.

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