title: Role of proprotein convertases in the pathogenic processing of the amyloidosis-associated form of secretory gelsolin.
abstract: Familial amyloidosis of the Finnish type (FAF) is caused by two proteolytic cleavages of mutant gelsolin leading to the accumulation of FAF amyloid in the patients' tissues. Here, we demonstrate that, in mouse pituitary corticotropic AtT20 cells, the enzyme responsible for the first cleavage of mutant secretory FAF gelsolin to FAF amyloid precursor is present in reasonable amounts. Furthermore, in At T20 cells stably expressing alpha1-PDX a potent inhibitor of most proprotein convertases, this cleavage was inhibited The present data provide strong evidence that proprotein convertases, possibly furin or PC5, are involved in the initialpathological cleavage of mutant secretory FAF gelsolin leading ultimately to the amyloid disease.
authors.affiliation: Biomedicum Helsinki, Department of Molecular Medicine, National Public Health Institute, Finland. Hannele.Kangas@ktl.fi
authors.forename: Hannele
authors.initials: H
authors.lastname: Kangas
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D028226:Amyloidosis, Familial / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D045683:Furin; D018260:Gelsolin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D010902:Pituitary Gland / Q000166:cytology / Q000201:enzymology*; D043484:Proprotein Convertases; D013381:Subtilisins / Q000037:antagonists & inhibitors / Q000502:physiology*; D014162:Transfection; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
chemical_list: D000682:Amyloid; D018260:Gelsolin; D000515:alpha 1-Antitrypsin; C113421:alpha 1-antitrypsin Portland; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin