Complex contributions of fibronectin to initiation and maturation of microfibrils.
Fibrillins constitute the backbone of extracellular multifunctional assemblies present in elastic and non-elastic matrices, termed microfibrils. Assembly of fibrillins into microfibrils and their homoeostasis is poorly understood and is often compromised in connective tissue disorders such as Marfan syndrome and other fibrillinopathies. Using interaction mapping studies, we demonstrate that fibrillins require the complete gelatin-binding region of fibronectin for interaction, which comprises domains FNI6-FNI9. However, the interaction of fibrillin-1 with the gelatin-binding domain of fibronectin is not involved in fibrillin-1 network assembly mediated by human skin fibroblasts. We show further that the fibronectin network is essential for microfibril homoeostasis in early stages. Fibronectin is present in extracted mature microfibrils from tissue and cells as well as in some in situ microfibrils observed at the ultrastructural level, indicating an extended mechanism for the involvement of fibronectin in microfibril assembly and maturation.
*Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada, H3A 0C7.
Laetitia
L
Sabatier
Jelena
J
Djokic
Christine
C
Fagotto-Kaufmann
Marian
M
Chen
Douglas S
DS
Annis
Deane F
DF
Mosher
Dieter P
DP
Reinhardt
D018829:Adhesins, Bacterial / Q000737:chemistry; D000293:Adolescent; D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007223:Infant; D020894:Microfibrils / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D021381:Protein Transport; D054392:Adipokines
D018829:Adhesins, Bacterial; D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines