Ninjurin, a Novel Adhesion Molecule, Is Induced by Nerve Injury and Promotes Axonal Growth

Peripheral nerve injury results in axonal degeneration and in phenotypic changes of the surrounding Schwann cells, whose presence is critical for nerve regeneration. Using differential screening strategies, we identified a novel protein, termed ninjurin (for nerve injury-induced protein), that is up-regulated after axotomy in neurons and in Schwann cells surrounding the distal nerve segment. Ninjurin is located on the cell surface, is capable of mediating homophilic adhesion, and promotes neurite extension of dorsal root ganglion neurons in vitro. Ninjurin is also expressed in a number of other tissues, predominantly in epithelial cells. These results suggest that ninjurin plays a role in nerve regeneration and in the formation and function of other tissues.

[1]  M. Takeichi,et al.  Cadherin cell adhesion receptors as a morphogenetic regulator. , 1991, Science.

[2]  P. Morell,et al.  Lipid Metabolism During Early Stages of Wallerian Degeneration in the Rat Sciatic Nerve , 1989, Journal of neurochemistry.

[3]  A. Aguayo,et al.  Extensive elongation of axons from rat brain into peripheral nerve grafts , 1982, Nature.

[4]  M. Kanehisa,et al.  A knowledge base for predicting protein localization sites in eukaryotic cells , 1992, Genomics.

[5]  F. Walsh,et al.  Neuronal process outgrowth of human sensory neurons on monolayers of cells transfected with cDNAs for five human N-CAM isoforms , 1989, The Journal of cell biology.

[6]  M. E. Eichler,et al.  Death of sensory ganglion neurons after acute withdrawal of nerve growth factor in dissociated cell cultures , 1989, Brain Research.

[7]  J. Schweitzer,et al.  Expression of nerve growth factor receptors by Schwann cells of axotomized peripheral nerves: ultrastructural location, suppression by axonal contact, and binding properties , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  P. Distefano,et al.  Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation , 1988, The Journal of cell biology.

[9]  Eugene M. Johnson,et al.  Localization of FGF receptor mRNA in the adult rat central nervous system by in situ hybridization , 1990, Neuron.

[10]  S. Hall.  THE EFFECT OF INHIBITING SCHWANN CELL MITOSIS ON THE RE‐INNERVATION OF ACELLULAR AUTOGRAFTS IN THE PERIPHERAL NERVOUS SYSTEM OF THE MOUSE , 1986, Neuropathology and applied neurobiology.

[11]  M. Takeichi,et al.  Functional correlation between cell adhesive properties and some cell surface proteins , 1977, The Journal of cell biology.

[12]  J. Bixby,et al.  Distinct molecular interactions mediate neuronal process outgrowth on non-neuronal cell surfaces and extracellular matrices , 1986, The Journal of cell biology.

[13]  E. Shooter,et al.  Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13) , 1992, The Journal of cell biology.

[14]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[15]  Vance Lemmon,et al.  L1-mediated axon outgrowth occurs via a homophilic binding mechanism , 1989, Neuron.

[16]  P. Hauer,et al.  Axonal regulation of myelin protein mRNA levels in actively myelinating Schwann cells , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  K. Horgan,et al.  Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. , 1990, Nature.

[18]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[19]  G. Edelman,et al.  Distribution and role in regeneration of N-CAM in the basal laminae of muscle and Schwann cells , 1988, The Journal of cell biology.

[20]  J. Milbrandt,et al.  The NGFI-B protein, an inducible member of the thyroid/steroid receptor family, is rapidly modified posttranslationally , 1990, Molecular and cellular biology.

[21]  J. Bixby,et al.  Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro , 1988, The Journal of cell biology.

[22]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[23]  C. Brewer.  Chapter 11 Cytomegalovirus Plasmid Vectors for Permanent Lines of Polarized Epithelial Cells , 1994 .

[24]  J. Fallon.  Neurite guidance by non-neuronal cells in culture: preferential outgrowth of peripheral neurites on glial as compared to nonglial cell surfaces , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  B. Hoffman,et al.  A simple and very efficient method for generating cDNA libraries. , 1983, Gene.

[26]  G. Edelman,et al.  Altered expression of neuronal cell adhesion molecules induced by nerve injury and repair , 1986, The Journal of cell biology.

[27]  G. Rougon,et al.  Transfected F3/F11 neuronal cell surface protein mediates intercellular adhesion and promotes neurite outgrowth , 1991, Neuron.

[28]  M. Schachner,et al.  Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture , 1988, The Journal of cell biology.

[29]  D. Steindler,et al.  The Complex Nature of Interactive Neuroregeneration-Related Molecules , 1993, Experimental Neurology.

[30]  Singer Sj.  The Structure and Insertion of Integral Proteins in Membranes , 1990 .

[31]  J. Thompson,et al.  Selective radiolabeling of cell surface proteins to a high specific activity. , 1987, Biochemistry.

[32]  A. Aguayo,et al.  Axons from CNS neurones regenerate into PNS grafts , 1980, Nature.

[33]  C. Brewer.  Cytomegalovirus plasmid vectors for permanent lines of polarized epithelial cells. , 1994, Methods in cell biology.

[34]  J. Milbrandt,et al.  Growth and Differentiation Proceeds Normally in Cells Deficient in the Immediate Early Gene NGFI-A (*) , 1995, The Journal of Biological Chemistry.

[35]  J. Rubenstein,et al.  Subtractive hybridization system using single-stranded phagemids with directional inserts. , 1990, Nucleic acids research.

[36]  S. Singer.  The structure and insertion of integral proteins in membranes. , 1990, Annual review of cell biology.

[37]  J W Fawcett,et al.  Peripheral nerve regeneration. , 1990, Annual review of neuroscience.

[38]  B. Rost,et al.  Transmembrane helices predicted at 95% accuracy , 1995, Protein science : a publication of the Protein Society.

[39]  R. Martini.  Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves , 1994, Journal of neurocytology.