Cited by 20Axon Guidance and Neuronal SignalingNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

Reciprocal Regulation of Very Low Density Lipoprotein Receptors (VLDLRs) in Neurons by Brain-derived Neurotrophic Factor (BDNF) and Reelin

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Do, Hai Thi, Bruelle, Céline, Tselykh, Timofey, Jalonen, Pilvi, Korhonen, Laura, Lindholm, Dan·2013·Journal of Biological Chemistry

Abstract

BDNF positively influences various aspects of neuronal migration, maturation, and survival in the developing brain. Reelin in turn mediates inhibitory signals to migrating neuroblasts, which is crucial for brain development. The interplay between BDNF and Reelin signaling in neurodevelopment is not fully understood. We show here that BDNF increased the levels of the Reelin receptor (VLDL receptor (VLDLR)) in hippocampal neurons by increasing gene expression. In contrast, Reelin decreased VLDLRs, which was accompanied by an increase in the levels of the E3 ligase Mylip/Idol in neurons. Down-regulation of Mylip/Idol using shRNAs abrogated the decrease in VLDLRs induced by Reelin. These results show that VLDLRs are tightly regulated in hippocampal neurons by both transcriptional and post-transcriptional mechanisms. The regulation of VLDLR by BDNF and Reelin may affect the migration of neurons and contribute to neurodevelopmental disorders in the nervous system. Background: VLDLR is a receptor for Reelin in brain neurons, but its mode of regulation is unclear. Results: BDNF increases VLDLR gene expression in hippocampal neurons, whereas Reelin decreases the receptor post-transcriptionally. Conclusion: Reelin down-regulates VLDLR via the E3 ubiquitin ligase Mylip/Idol. Significance: The dynamic regulation of VLDLR by BDNF and Reelin may be important for neuronal migration and brain development.

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Crossref · 10.1074/jbc.m113.500967

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Authors
Do, H. T., Bruelle, C., Tselykh, T., Jalonen, P., Korhonen, L., & Lindholm, D.
Affiliations
  • University of Helsinki (FI)
  • Minerva Foundation (FI)
Corresponding author
Lindholm, Dan
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2013-10
Volume
288
Issue
41
Pages
29613-29620
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2138367192
Cited by
20
References
47
Citations by year
2024: 1 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 3 · 2016: 4 · 2015: 1 · 2014: 3
FWCI
1.31
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
VLDLR, brain-derived neurotrophic factor, reelin, E3 ubiquitin ligase, hippocampal neurons, brain development, neuronal migration, post-transcriptional regulation, transcriptional regulation, neurodevelopmental disorders
MeSH terms
Reelin Protein, Animals, Cells, Cultured, Hippocampus, Nerve Tissue Proteins, Neurons, Receptors, LDL, Serine Endopeptidases, Immunoblotting, Down-Regulation, Cell Adhesion Molecules, Neuronal, Gene Expression, Extracellular Matrix Proteins, Rats, Wistar, Brain-Derived Neurotrophic Factor, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Ubiquitin-Protein Ligases, Ubiquitination

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