Formation of granular cytoplasmic aggregates in COS7 cells expressing mutant Cu/Zn superoxide dismutase associated with familial amyotrophic lateral sclerosis.
To investigate the molecular mechanisms of the 'gain of toxic function' of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (Ala 4 --> Thr, Gly 85 --> Arg, Gly 93 --> Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant (mt) Cu/Zn SODs, but not in cells expressing wt Cu/Zn SOD. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mt Cu/Zn SODs promote the formation of aggregates which are toxic to cells.
Koide
T
T
Department of Neurology, Brain Research Institute, Niigata University, Japan.
Igarashi
S
S
Kikugawa
K
K
Nakano
R
R
Inuzuka
T
T
Yamada
M
M
Takahashi
H
H
Tsuji
S
S
D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D003593:Cytoplasm / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D015870:Gene Expression; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics*; D013997:Time Factors; D014162:Transfection
D013482:Superoxide Dismutase