PMID:12372286

Citation	Yue, Z, Horton, A, Bravin, M, DeJager, PL, Selimi, F and Heintz, N (2002) A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice. Neuron 35:921-33
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 GluRdelta2 that results in its constitutive activation. Here we have identified protein interactions between GluRdelta2, 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. GluRdelta2(Lc), but not GluRdelta2(wt), 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 GluRdelta2(Lc) receptor and stimulation of the autophagic pathway in dying lurcher Purkinje cells.
Links	PubMed
Keywords	Animals; Apoptosis Regulatory Proteins; Autophagy/physiology; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Cell Death/physiology; Humans; Membrane Proteins; Mice; Mice, Neurologic Mutants; Neurodegenerative Diseases/metabolism; Neurodegenerative Diseases/pathology; Protein Isoforms/chemistry; Protein Isoforms/metabolism; Proteins/chemistry; Proteins/metabolism; Purkinje Cells/metabolism; Purkinje Cells/pathology; Receptors, Glutamate/chemistry; Receptors, Glutamate/metabolism
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