Fibronectin attenuates process outgrowth in oligodendrocytes by mislocalizing MMP-9 activity.
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.
Sisková
Zuzana
Z
Department of Cell Biology, Section Membrane Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
Yong
V Wee
VW
Nomden
Anita
A
van Strien
Miriam
M
Hoekstra
Dick
D
Baron
Wia
W
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
D017077:Culture Media, Conditioned; D005353:Fibronectins; D011493:Protein Kinase C; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9