Soluble β-amyloid Precursor Protein Alpha binds to p75 neurotrophin receptor to promote neurite outgrowth

PloS One
Noriko HasebeToshihide Yamashita

Abstract

The cleavage of β-amyloid precursor protein (APP) generates multiple proteins: Soluble β-amyloid Precursor Protein Alpha (sAPPα), sAPPβ, and amyloid β (Aβ). Previous studies have shown that sAPPα and sAPPβ possess neurotrophic properties, whereas Aβ is neurotoxic. However, the underlying mechanism of the opposing effects of APP fragments remains poorly understood. In this study, we have investigated the mechanism of sAPPα-mediated neurotrophic effects. sAPPα and sAPPβ interact with p75 neurotrophin receptor (p75(NTR)), and sAPPα promotes neurite outgrowth. First, we investigated whether APP fragments interact with p75(NTR), because full-length APP and Aβ have been shown to interact with p75(NTR) in vitro. Both sAPPα and sAPPβ were co-immunoprecipitated with p75(NTR) and co-localized with p75(NTR) on COS-7 cells. The binding affinity of sAPPα and sAPPβ for p75(NTR) was confirmed by enzyme-linked immunosorbent assay (ELISA). Next, we investigated the effect of sAPPα on neurite outgrowth in mouse cortical neurons. Neurite outgrowth was promoted by sAPPα, but sAPPα was uneffective in a knockdown of p75(NTR). We conclude that p75(NTR) is the receptor for sAPPα to mediate neurotrophic effects.

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Citations

Jan 7, 2015·Molecular Neurobiology·Yanuar Alan Sulistio, Klaus Heese
Feb 4, 2016·Trends in Pharmacological Sciences·Carole DeytsAngèle T Parent
Oct 27, 2015·Cellular Signalling·Stephen P Duggan, Justin V McCarthy
Jan 4, 2017·Bioorganic & Medicinal Chemistry·Jutamas JiaranaikulwanitchOpa Vajragupta
Jul 16, 2017·The Journal of Endocrinology·Joshua A KulasColin K Combs
Apr 21, 2018·The Journal of Endocrinology·Juliane K CzeczorSean L McGee
Feb 19, 2020·Translational Psychiatry·Balmiki RayDebomoy K Lahiri
Jul 1, 2020·Journal of Alzheimer's Disease : JAD·Maria ChatzistavrakiSpiros Efthimiopoulos
May 26, 2018·Molecular Neurobiology·Noralyn Basco Mañucat-TanXin-Fu Zhou
Jan 22, 2020·Cellular and Molecular Life Sciences : CMLS·Nawab John Dar, Gordon W Glazner
Apr 21, 2018·Molecular Neurobiology·Luan LuuRoberto Cappai
Aug 18, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Rebecca E K MacPherson
Jun 6, 2017·Neurochemistry International·Scott J Koppel, Russell H Swerdlow

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Methods Mentioned

BETA
electrophoresis
transfection
pull-down
ELISA

Software Mentioned

ImageJ
image J

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