Skip to Main content Skip to Navigation
Journal articles

Alix, making a link between apoptosis-linked gene-2, the endosomal sorting complexes required for transport, and neuronal death in vivo.

Abstract : Alix/apoptosis-linked gene-2 (ALG-2)-interacting protein X is an adaptor protein involved in the regulation of the endolysosomal system through binding to endophilins and to endosomal sorting complexes required for transport (ESCRT) proteins, TSG101 and CHMP4b. It was first characterized as an interactor of ALG-2, a calcium-binding protein necessary for cell death, and several observations suggest a role for Alix in controlling cell death. We used electroporation in the chick embryo to test whether overexpressed wild-type or mutated Alix proteins influence cell death in vivo. We show that Alix overexpression is sufficient to induce cell death of neuroepithelial cells. This effect is strictly dependent on its capacity to bind to ALG-2. On the other hand, expression of Alix mutants lacking the ALG-2 or the CHMP4b binding sites prevents early programmed cell death in cervical motoneurons at day 4.5 of chick embryo development. This protection afforded by Alix mutants was abolished after deletion of the TSG101, but not of the endophilin, binding sites. Our results suggest that the interaction of the ALG-2/Alix complex with ESCRT proteins is necessary for naturally occurring death of motoneurons. Therefore, Alix represents a molecular link between the endolysosomal system and the cell death machinery.
Complete list of metadatas

Cited literature [38 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00381816
Contributor : Sandrine Fraboulet <>
Submitted on : Wednesday, July 13, 2011 - 10:08:18 AM
Last modification on : Friday, November 6, 2020 - 3:48:31 AM
Long-term archiving on: : Friday, October 14, 2011 - 2:20:06 AM

File

Mahul_et_al_2006.pdf
Publisher files allowed on an open archive

Identifiers

Collections

U836 | UGA

Citation

Anne-Laure Mahul-Mellier, Fiona Hemming, Béatrice Blot, Sandrine Fraboulet, Rémy Sadoul. Alix, making a link between apoptosis-linked gene-2, the endosomal sorting complexes required for transport, and neuronal death in vivo.. Journal of Neuroscience, Society for Neuroscience, 2006, 26 (2), pp.542-9. ⟨10.1523/JNEUROSCI.3069-05.2006⟩. ⟨inserm-00381816⟩

Share

Metrics

Record views

356

Files downloads

421