[HTML][HTML] F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation

QD Hu, BT Ang, M Karsak, WP Hu, XY Cui, T Duka… - Cell, 2003 - cell.com
QD Hu, BT Ang, M Karsak, WP Hu, XY Cui, T Duka, Y Takeda, W Chia, N Sankar, YK Ng
Cell, 2003cell.com
Axon-derived molecules are temporally and spatially required as positive or negative
signals to coordinate oligodendrocyte differentiation. Increasing evidence suggests that, in
addition to the inhibitory Jagged1/Notch1 signaling cascade, other pathways act via Notch to
mediate oligodendrocyte differentiation. The GPI-linked neural cell recognition molecule
F3/contactin is clustered during development at the paranodal region, a vital site for axoglial
interaction. Here, we show that F3/contactin acts as a functional ligand of Notch. This trans …
Abstract
Axon-derived molecules are temporally and spatially required as positive or negative signals to coordinate oligodendrocyte differentiation. Increasing evidence suggests that, in addition to the inhibitory Jagged1/Notch1 signaling cascade, other pathways act via Notch to mediate oligodendrocyte differentiation. The GPI-linked neural cell recognition molecule F3/contactin is clustered during development at the paranodal region, a vital site for axoglial interaction. Here, we show that F3/contactin acts as a functional ligand of Notch. This trans-extracellular interaction triggers γ-secretase-dependent nuclear translocation of the Notch intracellular domain. F3/Notch signaling promotes oligodendrocyte precursor cell differentiation and upregulates the myelin-related protein MAG in OLN-93 cells. This can be blocked by dominant negative Notch1, Notch2, and two Deltex1 mutants lacking the RING-H2 finger motif, but not by dominant-negative RBP-J or Hes1 antisense oligonucleotides. Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination.
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