title: Fibronectin attenuates process outgrowth in oligodendrocytes by mislocalizing MMP-9 activity.
abstract: The extension of multiple oligodendroglial branched processes towards axons is an important event during the early stages of myelination that likely requires remodeling of the extracellular matrix (ECM) microenvironment via matrix metalloproteinases (MMPs). Here we investigated whether fibronectin-mediated inhibition of myelin sheet formation in oligodendrocytes correlated with an altered MMP activity. Our data reveal that fibronectin enhanced, in a PKC-dependent manner, the net activity of MMP-9, but not its expression, in conditioned medium of oligodendrocytes. Residual cellular MMP-9 activity on fibronectin was confined to the cell body, whereas MMP-9 activity on laminin-2 was localized along extending processes of oligodendrocytes. The mislocalization of MMP-9 activity on fibronectin correlated with a perturbed outgrowth of oligodendroglial processes. In conclusion, our findings suggest that ECM molecules influence both the net activity of secreted MMP and the spatial distribution of cell-associated MMP activity, and thereby morphological oligodendrocyte differentiation.
authors.affiliation: Department of Cell Biology, Section Membrane Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sisková
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.forename: Anita
authors.initials: A
authors.lastname: Nomden
authors.forename: Miriam
authors.initials: M
authors.lastname: van Strien
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017077:Culture Media, Conditioned; D005353:Fibronectins; D011493:Protein Kinase C; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9