Myelin basic protein cleaves cell adhesion molecule L1 and promotes neuritogenesis and cell survival

David Lutz, Gabriele Loers, Ralf Kleene, Iris Oezen, Hardeep Kataria, Nainesh Katagihallimath, Ingke Braren, George Harauz, Melitta Schachner

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The cell adhesion molecule L1 is a Lewisx-carrying glycoprotein that plays important roles in the developing and adult nervous system. Here we show that myelin basic protein (MBP) binds to L1 in a Lewisx-dependent manner. Furthermore, we demonstrate that MBP is released by murine cerebellar neurons as a sumoylated dynamin-containing protein upon L1 stimulation and that this MBP cleaves L1 as a serine protease in the L1 extracellular domain at Arg 687 yielding a transmembrane fragment that promotes neurite outgrowth and neuronal survival in cell culture. L1-induced neurite outgrowth and neuronal survival are reduced in MBP-deficient cerebellar neurons and in wild-type cerebellar neurons in the presence of an MBP antibody or L1 peptide containing the MBP cleavage site. Genetic ablation of MBPin shiverer mice and mutagenesis of the proteolytically active site in MBP or of the MBP cleavage site within L1 as well as serine protease inhibitors and an L1 peptide containing the MBPcleavage site abolish generation of the L1 fragment. Our findings provide evidence for novel functions of MBPin the nervous system.

Original languageEnglish (US)
Pages (from-to)13503-13518
Number of pages16
JournalJournal of Biological Chemistry
Volume289
Issue number19
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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