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Furin-mediated cleavage of LRP1 and increase in ICD of LRP1 after cerebral ischemia and after exposure of cultured neurons to NMDA
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- The N-methyl-D-aspartate (NMDA) receptor has been implicated in several neurodegenerative diseases, including stroke. Low-density lipoprotein receptor-related protein 1 (LRP1) plays pivotal roles in endocytosis and signaling in the cell. Immature LRP1 is processed by furin in the trans-Golgi network (TGN) and transported to the cell surface as its mature form. Activation of mature LRP1 exerts a protective effect against glutamate-induced degeneration of the rat retinal ganglion cells, as was shown in our previous study. However, the roles of LRP1 in the pathogenesis of excitotoxic neuronal injuries remain to be determined. The aim of this present study was to achieve further insight into the pathophysiologic roles of LRP1 after excitotoxic neuronal injuries. Our findings are the first to demonstrate that LRP1 was significantly cleaved by furin after cerebral ischemia in rats as well as after exposure of cultured cortical neurons to NMDA. It was noteworthy that the intracellular domain (ICD) of LRP1 was co-localized with TGN and furin. Furthermore, a furin inhibitor inhibited the cleavage of LRP1 and co-localization of LRP1-ICD with TGN or furin. Our findings suggest that furin-mediated cleavage of LRP1 and changes in the localization of LRP1-ICD were involved in the excitotoxic neuronal injury.
- Subjects :
- 0301 basic medicine
N-Methylaspartate
Cell death in the nervous system
Cell
lcsh:Medicine
Endocytosis
Retinal ganglion
Article
Brain Ischemia
Pathogenesis
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Humans
lcsh:Science
Receptor
Furin
Neurons
Multidisciplinary
biology
Chemistry
lcsh:R
Neurodegenerative Diseases
LRP1
Cellular neuroscience
Rats
Cell biology
Stroke
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Receptors, LDL
biology.protein
NMDA receptor
lcsh:Q
Low Density Lipoprotein Receptor-Related Protein-1
030217 neurology & neurosurgery
Signal Transduction
trans-Golgi Network
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....cb4a5505f20e1bc339ffde1ab267eedb