Tenascin‐R interferes with integrin‐dependent oligodendrocyte precursor cell adhesion by a ganglioside‐mediated signalling mechanism

Abstract

Oligodendrocyte (OL) lineage progression is characterized by the transient expression of the disialoganglioside GD3 by OL precursor (preOL) cells followed by the sequential expression of myelin-specific lipids and proteins. Whereas GD3+ preOLs are highly motile cells, the migratory capacity of OLs committed to terminal differentiation is strongly reduced, and we have recently shown that the extracellular matrix protein tenascin-R (TN-R) promotes the stable adhesion and differentiation of O4+ OLs by a sulphatide-mediated autocrine mechanism (O4 is a monoclonal antibody recognizing sulphatides/seminolipids expressed by OLs and in myelin). Using culture conditions that allow the isolation of mouse OLs at distinct lineage stages, here we demonstrate that TN-R is antiadhesive for GD3+ preOLs and inhibits their integrin-dependent adhesion to fibronectin (FN) by a disialoganglioside-mediated signalling mechanism affecting the tyrosine phosphorylation of the focal adhesion kinase. This responsive mechanism appears to be common to various cell types expressing disialogangliosides as: (i) disialogangliosides interfered with the inhibition of cell adhesion of different neural and non-neural cells on substrata containing TN-R and FN or RGD-containing FN fragments. TN-R interacted specifically with disialoganglioside-expressing cells or immobilized gangliosides, and ganglioside treatment of TN-R substrata resulted in a delayed preOL cell detachment as a function of time. We conclude that OL response to one and the same signal in the extracellular matrix critically depends on the molecular repertoire expressed by OLs at different lineage stages and could thus define their final positioning.

The extracellular matrix glycoprotein tenascin-R regulates neurogenesis during development and in the adult dentate gyrus of mice

“…TNR has been shown to associate with sodium channel b-subunits (Xiao et al, 1999), the cell surface receptor F3/contactin-1 (Pesheva et al, 1993), acetylated gangliosides (Probstmeier et al, 1999) and receptor protein tyrosine phosphatase (RPTP)-zeta/beta (Milev et al, 1998;Xiao et al, 1997). In addition, a cognate receptor interacting with TNR in NSCs is b1 integrin, which is a prominent sensor of signaling from extracellular matrix components expressed by neural cells (Liao et al, 2008).…”

Lactosylceramide Is Essential for the Osteoclastogenesis Mediated by Macrophage-Colony-stimulating Factor and Receptor Activator of Nuclear Factor-κB Ligand

“…54) and to modulate integrin-mediated adhesion (55,56). In neuronal cells, binding to disialogangliosides by tenascin or anti-GD2 antibody causes inhibition of protein kinase C and prevention of integrin-dependent adhesion to fibronectin, resulting in inhibition of neurite outgrowth (57,58). Therefore, GM1, which is not expressed in GM2/GD2-TϪ/Ϫ mice, increased after RANKL stimulation; this might be important to TRAP-positive mononuclear and multinuclear cell formation, especially for cell-to-cell attachment and fusion.…”

Myelin-associated Glycoprotein Interacts with Ganglioside GT1b

“…In neuronal cells, binding to disialogangliosides by tenascin-C, tenascin-R, or an anti-GD2 antibody causes inhibition of protein kinase C and prevention of integrin-dependent adhesion to fibronectin, resulting in inhibition of neurite outgrowth (37,67).…”