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 Dorard1,2 & Stéphanie Chasseigneaux1,3 & Lucie Gorisse-Hussonnois1 & Cédric Broussard4 & Thierry Pillot2 & Bernadette Allinquant1


1 /  UMR_S894 INSERM, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 75014 Paris, France
2 /  SynAging, 54500Vandoeuvre-les, Nancy, France
3 / INSERM U1144, Université Paris Descartes and Université Paris Diderot UMR-S 1144, 75006 Paris, France
4 / Plate-forme Protéomique, Université Paris Descartes 3P5, Institut Cochin, 75014 Paris, France # Springer Science+Business Media, LLC 2017

 


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 Nterminal 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


This part of the website could either be in French or English, depending on the sources of the actualities.

Autres Publications

 28 mai 2019
Kremen1-induced cell death is regulated by homo- and heterodimerization
 20 mai 2019
Impaired attentional modulation of sensorimotor control and cortical excitability in schizophrenia
 06 mai 2019
Routing Hippocampal Information Flow through Parvalbumin Interneuron Plasticity in Area CA2
 30 avril 2019
Individual recovery profiles of manual dexterity, and relation to corticospinal lesion load and excitability after stroke —a longitudinal pilot study
 11 avril 2019
Neuronal activity in vivo enhances functional myelin repair
 10 avril 2019
Somatostatin Serves a Modulatory Role in the Mouse Olfactory Bulb: Neuroanatomical and Behavioral Evidence
 13 février 2019
A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine
 11 février 2019
Live Tracking of Inter-organ Communication by Endogenous Exosomes In Vivo
 06 février 2019
Mitochondria, Metabolism, and Redox Mechanisms in Psychiatric Disorders
 09 janvier 2019
In vivo Optogenetic Approach to Study Neuron-Oligodendroglia Interactions in Mouse Pups
 21 décembre 2018
Predictive Modulation of Corticospinal Excitability and Implicit Encoding of Movement Probability in Schizophrenia
 07 novembre 2018
Manual Dexterity and Aging: A Pilot Study Disentangling Sensorimotor From Cognitive Decline
 05 novembre 2018
Burnout in medical students before residency: A systematic review and meta-analysis
 03 octobre 2018
Tobacco Smoking and Psychotic-Like Experiences in a General Population Sample
 14 juin 2018
The GABAergic Gudden's dorsal tegmental nucleus: A new relay for serotonergic regulation of sleep-wake behavior in the mouse
 07 juin 2018
a2- and b2-Adrenoreceptor-Mediated Efficacy of the Atypical Antidepressant Agomelatine Combined With Gabapentin to Suppress Allodynia in Neuropathic Rats With Ligated Infraorbital or Sciatic Nerve
 18 mai 2018
Memory circuits: CA2
 07 mai 2018
Cortical developmental death: selected to survive or fated to die
 05 avril 2018
Plasma amyloid levels within the Alzheimer’s process and correlations with central biomarkers
 02 mars 2018
Longitudinal Analyses of Blood Transcriptome During Conversion to Psychosis.