Fibrillin secretion and microfibril assembly by Marfan dermal fibroblasts.
The Marfan syndrome has been linked to the FBN1 gene encoding the microfibrillar glycoprotein fibrillin. To date, there have been no descriptions of microfibrillar abnormalities characteristic of this connective tissue disorder, although biochemical analyses have highlighted apparent abnormalities in fibrillin synthesis, secretion and processing. We have conducted a biochemical and ultrastructural investigation of fibrillin expression and assembly by a panel of dermal fibroblast lines from patients with Marfan syndrome and related diseases. The study has highlighted marked differences between cells in terms of secretion and aggregation of newly-synthesised fibrillin. In addition, electron microscopic visualization of fibrillin assemblies has clearly demonstrated for the first time the plethora of microfibrillar abnormalities that underlie this heterogeneous disorder. These data emphasize the molecular complexity that is a feature of the diverse clinical phenotypes exhibited by Marfan patients.
Kielty
C M
CM
School of Biological Sciences, University of Manchester, UK.
Phillips
J E
JE
Child
A H
AH
Pope
F M
FM
Shuttleworth
C A
CA
D001345:Autoradiography; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008382:Marfan Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000648:ultrastructure; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D008970:Molecular Weight; D012016:Reference Values; D012867:Skin / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D013462:Sulfur Radioisotopes; C000605722:FBN1 protein, human; D054392:Adipokines