title: Amyloid precursor protein at node of Ranvier modulates nodal formation.
abstract: Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination.
authors.affiliation: a Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases ; Institute of Neuroscience; the Second Affiliated Hospital; Soochow University ; Suzhou , China.
authors.forename: De-En
authors.initials: DE
authors.lastname: Xu
authors.forename: Wen-Min
authors.initials: WM
authors.lastname: Zhang
authors.forename: Zara Zhuyun
authors.initials: ZZ
authors.lastname: Yang
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhu
authors.forename: Ke
authors.initials: K
authors.lastname: Yan
authors.forename: Shao
authors.initials: S
authors.lastname: Li
authors.forename: Dominique
authors.initials: D
authors.lastname: Bagnard
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Dawe
authors.forename: Quan-Hong
authors.initials: QH
authors.lastname: Ma
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000502:physiology*; D002490:Central Nervous System; D003711:Demyelinating Diseases; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D017933:Peripheral Nervous System; D011901:Ranvier's Nodes / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology*; D015222:Sodium Channels; D013116:Spinal Cord / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015222:Sodium Channels; D019063:Tenascin; C074638:tenascin R
keywords: APP; myelination; nodes of Ranvier; paranode; sodium channels