1. The dependence receptor DCC requires lipid raft localization for cell death signaling
- Author
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Céline Furne, Véronique Corset, Nathalie Cahuzac, Patrick Mehlen, Anne-Odile Hueber, Zoltán Hérincs, Apoptose, cancer et développement (ACD), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
- Subjects
MESH: Signal Transduction ,Deleted in Colorectal Cancer ,MESH: Membrane Microdomains ,MESH: Neurons ,Apoptosis ,Dependence receptor ,MESH: Caspase 9 ,MESH: Recombinant Proteins ,0302 clinical medicine ,MESH: Animals ,Receptor ,Lipid raft ,Cells, Cultured ,MESH: Receptors, Cell Surface ,Neurons ,0303 health sciences ,Multidisciplinary ,Transfection ,Biological Sciences ,Netrin-1 ,DCC Receptor ,Caspase 9 ,Recombinant Proteins ,3. Good health ,Cell biology ,Caspases ,Signal transduction ,Signal Transduction ,MESH: Cells, Cultured ,Programmed cell death ,MESH: Rats ,Tumor suppressor gene ,Receptors, Cell Surface ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Cell Line ,03 medical and health sciences ,Membrane Microdomains ,Animals ,Humans ,MESH: Tumor Suppressor Proteins ,Nerve Growth Factors ,030304 developmental biology ,MESH: Caspases ,MESH: Humans ,MESH: Nerve Growth Factors ,Tumor Suppressor Proteins ,MESH: Apoptosis ,MESH: Transfection ,fungi ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Rats ,MESH: Cell Line ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2006
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