Nogo-A couples with Apg-1 through interaction and coordinate expression under hypoxic and oxidative stress

Nogo-A is the largest isoform of the Nogo/RTN4 proteins and has been characterized as a major myelin associated inhibitor of regenerative nerve growth in the adult central nervous system (CNS). 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 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 paralog 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. While both proteins were up-regulated under hypoxic conditions, their expression levels were reduced on the addition of hydrogen peroxide. Taken together, our data 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 ischemia, but also in neuroblastoma formation.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Biomolecules Source Type: research