Polyglutamine domain proteins with expanded repeats bind neurofilament, altering the neurofilament network.
Proteins with expanded polyglutamine (polyQ) repeats cause eight inherited neurodegenerative diseases. Nuclear and cytoplasmic polyQ protein is a common feature of these diseases, but its role in cell death remains debatable. Since the neuronal intermediate filament network is composed of neurofilament (NF) and NF abnormalities occur in neurodegenerative diseases, we examined whether pathologic-length polyQ domain proteins interact with NF. We expressed polyQ-green fluorescent fusion proteins (GFP) in a neuroblast cell line, TR1. Pathologic-length polyQ-GFP fusion proteins form large cytoplasmic aggregates surrounded by neurofilament. Immunoisolation of pathologic-length polyQ proteins co-isolated 68 kD NF protein demonstrating molecular interaction. These observations suggest that polyQ interaction with NF is important in the pathogenesis of the polyglutamine repeat diseases.
Nagai
Y
Y
Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 27710, USA.
Onodera
O
O
Strittmatter
W J
WJ
Burke
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009454:Neurofibrils / Q000378:metabolism* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology* / Q000648:ultrastructure; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D014162:Transfection
D008164:Luminescent Proteins; D016900:Neurofilament Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C097188:polyglutamine