F3/contactin acts as a functional ligand for notch during oligodendrocyte maturation

Qi Dong Hu, Beng Ti Ang, Meliha Karsak, Wei Ping Hu, Xiao Ying Cui, Tanya Duka, Yasuo Takeda, Wendy Chia, Natesan Sankar, Yee Kong Ng, Eng Ang Ling, Thomas Maciag, Deena Small, Radianna Trifonova, Raphael Kopan, Hideyuki Okano, Masato Nakafuku, Shigeru Chiba, Hisamaru Hirai, Jon C. AsterMelitta Schachner, Catherine J. Pallen, Kazutada Watanabe, Zhi Cheng Xiao

Research output: Contribution to journalArticle

269 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)163-175
Number of pages13
JournalCell
Volume115
Issue number2
DOIs
Publication statusPublished - 2003 Oct 17

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hu, Q. D., Ang, B. T., Karsak, M., Hu, W. P., Cui, X. Y., Duka, T., Takeda, Y., Chia, W., Sankar, N., Ng, Y. K., Ling, E. A., Maciag, T., Small, D., Trifonova, R., Kopan, R., Okano, H., Nakafuku, M., Chiba, S., Hirai, H., ... Xiao, Z. C. (2003). F3/contactin acts as a functional ligand for notch during oligodendrocyte maturation. Cell, 115(2), 163-175. https://doi.org/10.1016/S0092-8674(03)00810-9