title: Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System.
abstract: The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination. A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type-specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases.
authors.affiliation: From the Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf (GMzH, AD, FS, MS, CB, HCL, H-PH, BCK); and Department of Neuropathology, Georg-August-University (RS); and Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine (RS), Göttingen, Germany; and Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts (MT).
authors.forename: Gerd
authors.initials: G
authors.lastname: Meyer zu Horste
authors.forename: Angelika
authors.initials: A
authors.lastname: Derksen
authors.forename: Ruth
authors.initials: R
authors.lastname: Stassart
authors.forename: Fabian
authors.initials: F
authors.lastname: Szepanowski
authors.forename: Melissa
authors.initials: M
authors.lastname: Thanos
authors.forename: Mark
authors.initials: M
authors.lastname: Stettner
authors.forename: Christina
authors.initials: C
authors.lastname: Boettcher
authors.forename: Helmar C
authors.initials: HC
authors.lastname: Lehmann
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency* / Q000235:genetics; D000072197:ADAM10 Protein; D000200:Action Potentials / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001369:Axons / Q000502:physiology*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology; D018737:Hand Strength / Q000502:physiology; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000166:cytology*; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics; D009924:Organ Culture Techniques; D017933:Peripheral Nervous System / Q000166:cytology* / Q000502:physiology; D012584:Sciatic Nerve / Q000473:pathology / Q000648:ultrastructure; D020426:Sciatic Neuropathy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse