Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway

Jorge A. Larios, Ignacio Jausoro, Maria Luisa Benitez, Francisca C. Bronfman, Maria Paz Marzolo

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11 Citas (Scopus)


Background: ApoER2 and the neurotrophin receptors Trk and p75NTR are expressed in the CNS and regulate key functional aspects of neurons, including development, survival, and neuronal function. It is known that both ApoER2 and p75NTR are processed by metalloproteinases, followed by regulated intramembrane proteolysis. TrkA activation by nerve growth factor (NGF) increases the proteolytic processing of p75NTR mediated by ADAM17. Reelin induces the sheeding of ApoER2 ectodomain depending on metalloproteinase activity. However, it is not known if there is a common regulation mechanism for processing these receptors.Results: We found that TrkA activation by NGF in PC12 cells induced ApoER2 processing, which was dependent on TrkA activation and metalloproteinases. NGF-induced ApoER2 proteolysis was independent of mitogen activated protein kinase activity and of phosphatidylinositol-3 kinase activity. In contrast, the basal proteolysis of ApoER2 increased when both kinases were pharmacologically inhibited. The ApoER2 ligand reelin regulated the proteolytic processing of its own receptor but not of p75NTR. Finally, in primary cortical neurons, which express both ApoER2 and TrkB, we found that the proteolysis of ApoER2 was also regulated by brain-derived growth factor (BDNF).Conclusions: Our results highlight a novel relationship between neurotrophins and the reelin-ApoER2 system, suggesting that these two pathways might be linked to regulate brain development, neuronal survival, and some pathological conditions.

Idioma originalInglés
Número de artículo108
PublicaciónBMC Neuroscience
EstadoPublicada - 19 sep. 2014
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Neurociencias General
  • Neurociencia celular y molecular


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