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 familiar amyotrophi c 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-typ e (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observe d in cells expressing mutant (mt) Cu/Zn SODs, but not in cells expressing w t Cu/Zn SOD. The aggregates contained ribosome-like particles and endoplasm ic reticulum. These results suggest the possibility that mt Cu/Zn SODs prom ote the formation ol:aggregates which are toxic to cells. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.