title: Myelin Basic Protein Cleaves Cell Adhesion Molecule L1 and Improves Regeneration After Injury.
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.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Lutz
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Hardeep
authors.initials: H
authors.lastname: Kataria
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kleene
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Loers
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Harshita
authors.initials: H
authors.lastname: Chaudhary
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.|Department of Cellular Neurobiology, Medical School Hannover, Hannover, Germany.
authors.forename: Daria
authors.initials: D
authors.lastname: Guseva
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovcevski
authors.affiliation: Melitta Schachner, Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, China. schachner@stu.edu.cn.|Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ, 08854, USA. schachner@stu.edu.cn.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D001369:Axons / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation; D000229:Dependovirus / Q000378:metabolism; D005267:Femoral Nerve / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000473:pathology; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008970:Molecular Weight; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D000071446:Neuronal Outgrowth; D020127:Recovery of Function; D012583:Schwann Cells / Q000473:pathology; D013569:Synapses / Q000378:metabolism
chemical_list: D000906:Antibodies; D004676:Myelin Basic Protein; D039842:Neural Cell Adhesion Molecule L1
keywords: Cell adhesion molecule L1; Development; Myelin basic protein; Nerve injury; Regeneration; Spinal cord injury