title: Nogo-A couples with Apg-1 through interaction and co-ordinate expression under hypoxic and oxidative stress.
abstract: Nogo-A is the largest isoform of the Nogo/RTN4 (reticulon 4) proteins and has been characterized as a major myelin-associated inhibitor of regenerative nerve growth in the adult CNS (central nervous system). Apart from the myelin sheath, Nogo-A is expressed at high levels in principal neurons of the CNS. The specificity of Nogo-A resides in its central domain, NiG. We identified Apg-1, a member of the stress-induced Hsp110 (heat-shock protein of 110 kDa) family, as a novel interactor of NiG/Nogo-A. The interaction is selective because Apg-1 interacts with Nogo-A/RTN4-A, but not with RTN1-A, the closest paralogue of Nogo-A. Conversely, Nogo-A binds to Apg-1, but not to Apg-2 or Hsp105, two other members of the Hsp110 family. We characterized the Nogo-A-Apg-1 interaction by affinity precipitation, co-immunoprecipitation and proximity ligation assay, using primary hippocampal neurons derived from Nogo-deficient mice. Under conditions of hypoxic and oxidative stress we found that Nogo-A and Apg-1 were tightly co-regulated in hippocampal neurons. Although both proteins were up-regulated under hypoxic conditions, their expression levels were reduced upon the addition of hydrogen peroxide. Taken together, we suggest that Nogo-A is closely involved in the neuronal response to hypoxic and oxidative stress, an observation that may be of relevance not only in stroke-induced ischaemia, but also in neuroblastoma formation.
authors.affiliation: *Biocenter, Division of Neurobiochemistry, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
authors.forename: Ruslan I
authors.initials: RI
authors.lastname: Stanika
authors.forename: Bettina
authors.initials: B
authors.lastname: Sarg
authors.forename: Martin
authors.initials: M
authors.lastname: Offterdinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Hess
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
authors.forename: Herbert
authors.initials: H
authors.lastname: Lindner
authors.forename: Christine E
authors.initials: CE
authors.lastname: Bandtlow
authors.forename: Ludger
authors.initials: L
authors.lastname: Hengst
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Schweigreiter
mesh_terms: D000818:Animals; D016466:CHO Cells; D015687:Cell Hypoxia / Q000235:genetics; D003412:Cricetulus; D015536:Down-Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D000070798:Nogo Proteins; D018384:Oxidative Stress
chemical_list: D018840:HSP70 Heat-Shock Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; C099678:Hspa4l protein, mouse; C000603201:Rtn4 protein, mouse
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