Furin initiates gelsolin familial amyloidosis in the Golgi through a defect in Ca(2+) stabilization.
EMBO J
; 20(22): 6277-87, 2001 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-11707399
ABSTRACT
Hereditary familial amyloidosis of Finnish type (FAF) leading to amyloid in the peripheral and central nervous systems stems from deposition of a 71 residue fragment generated from the D187N/Y variants of plasma gelsolin by two sequential endoproteolytic events. We identify the protease accomplishing the first cleavage as furin, a proprotein convertase. Endoproteolysis of plasma gelsolin occurs in the trans-Golgi network due to the inability of the FAF variants to bind and be stabilized by Ca(2+). Secretion and processing of the FAF variants by furin can be uncoupled by blocking the convergence of the exocytic pathway transporting plasma gelsolin and the endocytic recycling of furin. We propose that coincidence of membrane trafficking pathways contributes to the development of proteolysis-initiated amyloid disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subtilisinas
/
Cálcio
/
Gelsolina
/
Amiloidose Familiar
/
Complexo de Golgi
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos