title: Focal adhesion kinase can play unique and opposing roles in regulating the morphology of differentiating oligodendrocytes.
abstract: During development cells of the oligodendrocyte lineage undergo significant changes in morphology when they differentiate from migratory oligodendrocyte progenitors, which are mostly bipolar, into post-migratory pre-myelinating oligodendrocytes, which extend complex and expanded process networks, and then finally into mature oligodendrocytes, which generate myelin sheaths required for efficient signal propagation within the nervous system. This extensive morphological remodeling occurs in the context of a complex extracellular environment and requires significant rearrangement of the cell's cytoskeleton. The molecular mechanisms underlying this intricate integration of signals, however, remain poorly understood. A key regulator of extracellular matrix to cytoskeleton signaling is the non-receptor tyrosine kinase FAK (focal adhesion kinase). Here, we report that FAK can regulate the morphology of differentiating post-migratory pre-myelinating oligodendrocytes in a unique and opposing fashion that is dependent on the nature of the extracellular matrix and mediated largely by FAK's catalytic activity. More specifically, FAK was found to restrict process network expansion in the presence of fibronectin but to promote morphological maturation in the presence of laminin-2. In addition, FAK's restraining role predominated for postnatal day 3-derived cells, while its maturation promoting role prevailed for postnatal day 5-derived cells. Taken together, our findings reveal a complex role of FAK in regulating the morphology of post-migratory pre-myelinating oligodendrocytes.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: Audrey D
authors.initials: AD
authors.lastname: Lafrenaye
authors.forename: Babette
authors.initials: B
authors.lastname: Fuss
mesh_terms: D000818:Animals; D002384:Catalysis; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology; D009836:Oligodendroglia / Q000201:enzymology* / Q000648:ultrastructure*; D015363:Quinolones / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology
chemical_list: C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; D004791:Enzyme Inhibitors; D005353:Fibronectins; D007797:Laminin; D015363:Quinolones; D034741:RNA, Small Interfering; D013450:Sulfones; C058783:laminin beta2; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases