The bacterial chaperonin GroEL requires GroES to reduce aggregation and cell death in a COS-7 cell model of Huntington's disease.
Huntington's disease (HD) is caused by expansions of more than 35 CAG repeats in the HD gene. These repeats are translated into a long polyglutamine tract that confers a deleterious gain-of-function on the mutant protein. Intraneuronal inclusions comprising mutant huntingtin are found in HD patient brains. Here we show that the bacterial chaperonin GroEL can reduce aggregation of mutant huntingtin in COS-7 cells and requires GroES for efficient activity, analogous to what has been described in bacteria. The reduction in aggregation of mutant huntingtin by GroEL/GroES was associated with protection against polyglutamine-induced cell death.
Carmichael
Jenny
J
Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
Vacher
Coralie
C
Rubinsztein
David C
DC
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D016923:Cell Death; D018835:Chaperonin 10 / Q000235:genetics / Q000378:metabolism*; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D014162:Transfection
D018835:Chaperonin 10; D018834:Chaperonin 60; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine