Physiological significance of proteolytic processing of Reelin revealed by cleavage-resistant Reelin knock-in mice.
Animals
Brain
/ metabolism
Cell Adhesion Molecules, Neuronal
/ genetics
Extracellular Matrix Proteins
/ genetics
Fluorescent Antibody Technique
Gene Expression
Gene Knock-In Techniques
Immunohistochemistry
Mice
Mice, Transgenic
Nerve Tissue Proteins
/ genetics
Proteolysis
Reelin Protein
Serine Endopeptidases
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 03 2020
11 03 2020
Historique:
received:
01
08
2019
accepted:
26
02
2020
entrez:
13
3
2020
pubmed:
13
3
2020
medline:
21
11
2020
Statut:
epublish
Résumé
Reelin is a secreted protein that plays versatile roles in neuronal development and function. The strength of Reelin signaling is regulated by proteolytic processing, but its importance in vivo is 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.
Identifiants
pubmed: 32161359
doi: 10.1038/s41598-020-61380-w
pii: 10.1038/s41598-020-61380-w
pmc: PMC7066138
doi:
Substances chimiques
Cell Adhesion Molecules, Neuronal
0
Extracellular Matrix Proteins
0
Nerve Tissue Proteins
0
Reelin Protein
0
Reln protein, mouse
EC 3.4.21.-
Serine Endopeptidases
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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