BACKGROUND: Mutations in calcium-responsive transactivator (CREST) encoding gene 
have been recently linked to ALS. Similar to several proteins implicated in ALS, 
CREST contains a prion-like domain and was reported to be a component of 
paraspeckles.
RESULTS: We demonstrate that CREST is prone to aggregation and co-aggregates 
with FUS but not with other two ALS-linked proteins, TDP-43 and TAF15, in 
cultured cells. Aggregation of CREST affects paraspeckle integrity, probably by 
trapping other paraspeckle proteins within aggregates. Like several other 
ALS-associated proteins, CREST is recruited to induced stress granules. Neither 
of the CREST mutations described in ALS alters its subcellular localization, 
stress granule recruitment or detergent solubility; however Q388stop mutation 
results in elevated steady-state levels and more frequent nuclear aggregation of 
the protein. Both wild-type protein and its mutants negatively affect neurite 
network complexity of unstimulated cultured neurons when overexpressed, with 
Q388stop mutation being the most deleterious. When overexpressed in the fly eye, 
wild-type CREST or its mutants lead to severe retinal degeneration without 
obvious differences between the variants.
CONCLUSIONS: Our data indicate that CREST and certain other ALS-linked proteins 
share several features implicated in ALS pathogenesis, namely the ability to 
aggregate, be recruited to stress granules and alter paraspeckle integrity. A 
change in CREST levels in neurons which might occur under pathological 
conditions would have a profound negative effect on neuronal homeostasis.