Myelin Basic Protein Cleaves Cell Adhesion Molecule L1 and Improves Regeneration After Injury

David Lutz, Hardeep Kataria, Ralf Kleene, Gabriele Loers, Harshita Chaudhary, Daria Guseva, Bin Wu, Igor Jakovcevski, Melitta Schachner

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Myelin basic protein (MBP) is a serine protease that cleaves neural cell adhesion molecule L1 and generates a transmembrane L1 fragment which facilitates L1-dependent functions in vitro, such as neurite outgrowth, neuronal cell migration and survival, myelination by Schwann cells as well as Schwann cell proliferation, migration, and process formation. Ablation and blocking of MBP or disruption of its proteolytic activity by mutation of a proteolytically active serine residue abolish L1-dependent cellular responses. In utero injection of adeno-associated virus encoding proteolytically active MBP into MBP-deficient shiverer mice normalizes differentiation, myelination, and synaptogenesis in the developing postnatal spinal cord, in contrast to proteolytically inactive MBP. Application of active MBP to the injured wild-type spinal cord and femoral nerve augments levels of a transmembrane L1 fragment, promotes remyelination, and improves functional recovery after injury. Application of MBP antibody impairs recovery. Virus-mediated expression of active MBP in the lesion site after spinal cord injury results in improved functional recovery, whereas injection of virus encoding proteolytically inactive MBP fails to do so. The present study provides evidence for a novel L1-mediated function of MBP in the developing spinal cord and in the injured adult mammalian nervous system that leads to enhanced recovery after acute trauma.

Original languageEnglish (US)
Pages (from-to)3360-3376
Number of pages17
JournalMolecular Neurobiology
Volume53
Issue number5
DOIs
StatePublished - Jul 1 2016

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Keywords

  • Cell adhesion molecule L1
  • Development
  • Myelin basic protein
  • Nerve injury
  • Regeneration
  • Spinal cord injury

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