Functional consequences of amyloidosis mutation for gelsolin polypeptide — analysis of gelsolin-actin interaction and gelsolin processing in gelsolin knock-out fibroblasts

Gelsolin, an actin-modulating protein, derived from a single gene exists in intracellular and secreted forms. A point mutation at position 187 of both forms of gelsolin causes familial amyloidosis of the Finnish type (FAF). Here, we expressed both isoforms of the wild-type and FAF mutant gelsolin in...

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Bibliographic Details
Published in:FEBS letters 1999-07, Vol.454 (3), p.233-239
Main Authors: Kangas, Hannele, Ulmanen, Ismo, Paunio, Tiina, Kwiatkowski, David J., Lehtovirta, Maarit, Jalanko, Anu, Peltonen, Leena
Format: Article
Language:English
Subjects:
Actin
Actins - metabolism
Amyloidosis
Amyloidosis - genetics
Amyloidosis - metabolism
Animals
Cells, Cultured
Fibroblasts - metabolism
Gelsolin
Gelsolin - genetics
Gelsolin - metabolism
Mice
Mice, Knockout
Mutation
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Summary:Gelsolin, an actin-modulating protein, derived from a single gene exists in intracellular and secreted forms. A point mutation at position 187 of both forms of gelsolin causes familial amyloidosis of the Finnish type (FAF). Here, we expressed both isoforms of the wild-type and FAF mutant gelsolin in mouse embryonic gelsolin-null fibroblasts. We demonstrate that the FAF mutation does not interfere with the normal actin-modulating function of intracellular gelsolin, and that aberrant processing of secreted FAF gelsolin to FAF amyloid precursor takes place in the gelsolin-negative background. These results suggest that, in patients with FAF, symptoms are caused by the accumulation in their tissues of amyloid derived from plasma gelsolin and are not due to functional differences in cytoplasmic gelsolin.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(99)00790-5