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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2006

The dependence receptor DCC requires lipid raft localization for cell death signaling.

Résumé

DCC (deleted in colorectal cancer) is a putative tumor suppressor gene whose expression is lost in numerous cancers. DCC also encodes the main receptor for the neuronal navigation cue netrin-1. It has been shown that DCC belongs to the so-called family of dependence receptors. Such receptors induce apoptosis when their ligand is absent, thus conferring a state of cellular dependence on ligand availability. We recently proposed that DCC is a tumor suppressor because it induces the death of tumor cells that grow in settings of ligand unavailability. Moreover, it seems that the DCC/netrin-1 pair may also regulate neuron survival during nervous system development. However, the mechanisms by which DCC triggers cell death are still unknown. We show here that the localization of DCC to lipid rafts is a prerequisite for its proapoptotic activity, both in immortalized cells and in primary neurons. The presence of DCC in lipid rafts probably allows the formation of an adequate submembrane complex, because the interaction of caspase-9 with DCC is inhibited by the disorganization of lipid rafts. Thus, dependence receptors may require lipid raft localization for cell death signaling.

Dates et versions

hal-00323529 , version 1 (22-09-2008)

Identifiants

Citer

Céline Furne, Véronique Corset, Zoltán Hérincs, Nathalie Cahuzac, Anne-Odile Hueber, et al.. The dependence receptor DCC requires lipid raft localization for cell death signaling.. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103 (11), pp.4128-33. ⟨10.1073/pnas.0507864103⟩. ⟨hal-00323529⟩
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