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Molecular Neurobiology

, Volume 55, Issue 7, pp 5594–5610 | Cite as

Soluble Amyloid Precursor Protein Alpha Interacts with alpha3-Na, K-ATPAse to Induce Axonal Outgrowth but Not Neuroprotection: Evidence for Distinct Mechanisms Underlying these Properties

  • Emilie Dorard
  • Stéphanie Chasseigneaux
  • Lucie Gorisse-Hussonnois
  • Cédric Broussard
  • Thierry Pillot
  • Bernadette Allinquant
Article
  • 216 Downloads

Abstract

Amyloid precursor protein (APP) is cleaved not only to generate the amyloid peptide (Aß), involved in neurodegenerative processes, but can also be metabolized by alpha secretase to produce and release soluble N-terminal APP (sAPPα), which has many properties including the induction of axonal elongation and neuroprotection. The mechanisms underlying the properties of sAPPα are not known. Here, we used proteomic analysis of mouse cortico-hippocampal membranes to identify the neuronal specific alpha3 (α3)-subunit of the plasma membrane enzyme Na, K-ATPase (NKA) as a new binding partner of sAPPα. We showed that sAPPα recruits very rapidly clusters of α3-NKA at neuronal surface, and its binding triggers a cascade of events promoting sAPPα-induced axonal outgrowth. The binding of sAPPα with α3-NKA was not observed for sAPPα-induced Aß1-42 oligomers neuroprotection, neither the downstream events particularly the interaction of sAPPα with APP before endocytosis, ERK signaling, and the translocation of SET from the nucleus to the plasma membrane. These data suggest that the mechanisms of the axonal growth promoting and neuroprotective properties of sAPPα appear to be specific and independent. The signals at the cell surface specific to trigger these mechanisms require further study.

Keywords

Soluble amyloid precursor protein alpha alpha3-Na, K-ATPase Neuron Axonal elongation Neuroprotection SET 

Notes

Acknowledgements

We thank Luc Camoin and François Guillonneau for their supervision and comments on the proteomic analysis. This work was supported by the Institut National de la Santé et de la Recherche Médicale, France and by SynAging, Nancy, France.

Compliance with Ethical Standards

The protocol of animal anesthesia was carried out in compliance with French law in strict accordance with the recommendations of the European Economic Committee (63/2010) and was approved by the local ethics committee (Direction Départementale des Services Vétérinaires de Paris, Service de la Protection de Santé Animale et de la Protection de l’Environnement).

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12035_2017_783_Fig11_ESM.gif (9 kb)
Fig. S1

Action of 1 nM ouabain on ATPase activity in primary neurons 1 nM of ouabain was added to primary neurons at 5DIV for 24 h. Neurons were then processed for ATPAse activity as described in Material and Methods. Data are expressed in μmol of Pi/h/mg proteins and are the mean ± SEM of 3 independent experiments. **: p < 0.01. (GIF 9 kb).

12035_2017_783_MOESM1_ESM.tif (123 kb)
High resolution image (TIFF 122 kb).

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.UMR_S894 INSERM, Université Paris Descartes, Sorbonne Paris CitéFaculté de MédecineParisFrance
  2. 2.SynAgingNancyFrance
  3. 3.INSERM U1144Université Paris Descartes and Université Paris Diderot UMR-S 1144ParisFrance
  4. 4.Plate-forme Protéomique, Université Paris Descartes 3P5Institut CochinParisFrance

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