A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice

Zhenyu Yue; Antony Horton; Monica Bravin; Philip L DeJager; Fekrije Selimi; Nathaniel Heintz

doi:10.1016/s0896-6273(02)00861-9

A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice

Neuron. 2002 Aug 29;35(5):921-33. doi: 10.1016/s0896-6273(02)00861-9.

Authors

Zhenyu Yue¹, Antony Horton, Monica Bravin, Philip L DeJager, Fekrije Selimi, Nathaniel Heintz

Affiliation

¹ Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

PMID: 12372286
DOI: 10.1016/s0896-6273(02)00861-9

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Apoptosis Regulatory Proteins
Autophagy / physiology*
Beclin-1
Carrier Proteins / chemistry
Carrier Proteins / metabolism
Cell Death / physiology
Golgi Matrix Proteins
Humans
Membrane Proteins*
Membrane Transport 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*

Substances

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
BECN1 protein, human
Beclin-1
Becn1 protein, mouse
Carrier Proteins
GOPC protein, human
Golgi Matrix Proteins
Membrane Proteins
Membrane Transport Proteins
Protein Isoforms
Proteins
Receptors, Glutamate
glutamate receptor delta 2