Neuron
Volume 35, Issue 5, 29 August 2002, Pages 921-933
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Article
A Novel Protein Complex Linking the δ2 Glutamate Receptor and Autophagy: Implications for Neurodegeneration in Lurcher Mice

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Abstract

Autophagy is a pathway for bulk degradation of subcellular constituents that is hyperactivated in many neurodegenerative conditions. It has been considered a second form of programmed cell death. Death of cerebellar Purkinje cells in lurcher animals is due to a mutation in GluRδ2 that results in its constitutive activation. Here we have identified protein interactions between GluRδ2, a novel isoform of a PDZ domain-containing protein (nPIST) that binds to this receptor, and Beclin1. nPIST and Beclin1 can synergize to induce autophagy. GluRδ2Lc, but not GluRδ2wt, can also induce autophagy. Furthermore, dying lurcher Purkinje cells contain morphological hallmarks of autophagic death in vivo. These results provide strong evidence that a direct link exists between GluRδ2Lc receptor and stimulation of the autophagic pathway in dying lurcher Purkinje cells.

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These authors contributed equally to this work.