Back to Search
Start Over
Physiological significance of proteolytic processing of Reelin revealed by cleavage-resistant Reelin knock-in mice
- Source :
- Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020), Scientific Reports
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- Reelin is a secreted protein that plays versatile roles in neuronal development and function, and hypoactivity of Reelin is implicated in many neuropsychiatric disorders. The strength of Reelin signaling is regulated by proteolytic processing, but its importancein vivois not yet fully understood. Here, we generated Reelin knock-in (PA-DV KI) mice in which the key cleavage site of Reelin was abolished by mutation. As expected, the cleavage of Reelin was severely abrogated in the cerebral cortex and hippocampus of PA-DV KI mice. The amount of Dab1, whose degradation is induced by Reelin signaling, decreased in these tissues, indicating that the signaling strength of Reelin was augmented. The brains of PA-DV KI mice were largely structurally normal, but unexpectedly, the hippocampal layer was disturbed. This phenotype was ameliorated in hemizygote PA-DV KI mice, indicating that excess Reelin signaling is detrimental to hippocampal layer formation. The neuronal dendrites of PA-DV KI mice had more branches and were elongated compared to wild-type mice. These results present the first direct evidence of the physiological importance of Reelin cleavage and suggest that inhibition of Reelin cleavage would counteract neuropsychiatric disorders without causing severe systemic side effects.
- Subjects :
- Cell Adhesion Molecules, Neuronal
Fluorescent Antibody Technique
Gene Expression
lcsh:Medicine
Mice, Transgenic
Nerve Tissue Proteins
Hippocampal formation
Cleavage (embryo)
Biochemistry
Article
Mice
In vivo
Gene knockin
Biophysical chemistry
medicine
Animals
Reelin
Gene Knock-In Techniques
lcsh:Science
Extracellular Matrix Proteins
Multidisciplinary
biology
Chemistry
Serine Endopeptidases
lcsh:R
Brain
Development of the nervous system
DAB1
Phenotype
Immunohistochemistry
Cell biology
Reelin Protein
medicine.anatomical_structure
nervous system
Cerebral cortex
Proteolysis
biology.protein
lcsh:Q
Hypoactivity
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....b150d68d8ddbc8e811d1f5bf32232c26
- Full Text :
- https://doi.org/10.1038/s41598-020-61380-w