Reciprocal Regulation of Very Low Density Lipoprotein Receptors (VLDLRs) in Neurons by Brain-derived Neurotrophic Factor (BDNF) and Reelin
Open accessAbstract
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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Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · see citing works
Trk Receptors: Roles in Neuronal Signal Transduction
Huang, E. J., & Reichardt, L. F. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161629 · Cited by 2,537 · see citing works
Molecular cloning and expression of brain-derived neurotrophic factor
Leibrock, J., Lottspeich, F., Hohn, A., Hofer, M., Hengerer, B., Masiakowski, P., Thoenen, H., & Barde, Y. (1989) · Nature · doi:10.1038/341149a0 · Cited by 1,458 · see citing works
Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.
Korte, M., Carroll, P., Wolf, E., Brem, G., Thoenen, H., & Bonhoeffer, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8856 · Cited by 1,426 · see citing works
Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders
Autry, A. E., & Monteggia, L. M. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.005108 · Cited by 1,390 · see citing works
Trommsdorff, M., Gotthardt, M., Hiesberger, T., Shelton, J., Stockinger, W., Nimpf, J., Hammer, R. E., Richardson, J. A., & Herz, J. (1999) · Cell · doi:10.1016/s0092-8674(00)80782-5 · Cited by 1,261 · see citing works
Hiesberger, T., Trommsdorff, M., Howell, B. W., Goffinet, A., Mumby, M. C., Cooper, J. A., & Herz, J. (1999) · Neuron · doi:10.1016/s0896-6273(00)80861-2 · Cited by 916 · see citing works
Zafra, F., Hengerer, B., Leibrock, J., Thoenen, H., & Lindholm, D. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07564.x · Cited by 897 · see citing works
Self-citationAutosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations
Hong, S. E., Shugart, Y. Y., Huang, D. T.-C., Shahwan, S. A., Grant, P. E., Hourihane, J. O., Martin, N. D. T., & Walsh, C. A. (2000) · Nature Genetics · doi:10.1038/79246 · Cited by 878 · see citing works
LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor
Zelcer, N., Hong, C., Boyadjian, R., & Tontonoz, P. (2009) · Science · doi:10.1126/science.1168974 · Cited by 848 · see citing works
Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation
Haglund, K., Sigismund, S., Polo, S., Szymkiewicz, I., Fiore, P. P. D., & Đikić, I. (2003) · Nature Cell Biology · doi:10.1038/ncb983 · Cited by 813 · see citing works
Reelin Is a Ligand for Lipoprotein Receptors
D'Arcangelo, G., Homayouni, R., Keshvara, L., Rice, D. S., Sheldon, M., & Curran, T. (1999) · Neuron · doi:10.1016/s0896-6273(00)80860-0 · Cited by 808 · see citing works
Sairanen, M., Lucas, G., Ernfors, P., Castrén, M., & Castrén, E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3741-04.2005 · Cited by 763 · see citing works
A decrease of reelin expression as a putative vulnerability factor in schizophrenia
Impagnatiello, F., Guidotti, A. R., Pesold, C., Dwivedi, Y., Caruncho, H. J., Pisu, M. G., Uzunov, D. P., Smalheiser, N. R., Davis, J. M., Pandey, G. N., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15718 · Cited by 753 · see citing works
Tissir, F., & Goffinet, A. M. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1113 · Cited by 748 · see citing works
Role of the Reelin Signaling Pathway in Central Nervous System Development
Rice, D. S., & Curran, T. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1005 · Cited by 667 · see citing works
Zafra, F., Ċastrén, E., Thoenen, H., & Lindholm, D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.22.10037 · Cited by 580 · see citing works
Self-citationReelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524 · see citing works
Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex.
Castrén, E., Zafra, F., Thoenen, H., & Lindholm, D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.20.9444 · Cited by 513 · see citing works
Self-citationA role for Cajal–Retzius cells and reelin in the development of hippocampal connections
Del Río, J. A., Heimrich, B., Borrell, V., Förster, E., Drakew, A., Alcántara, S., Nakajima, K., Miyata, T., Ogawa, M., Mikoshiba, K., et al. (1997) · Nature · doi:10.1038/385070a0 · Cited by 472 · see citing works
Reelin Activates Src Family Tyrosine Kinases in Neurons
Bock, H. H., & Herz, J. (2003) · Current Biology · doi:10.1016/s0960-9822(02)01403-3 · Cited by 355 · see citing works
Mouse disabled (mDab1): a Src binding protein implicated in neuronal development
Howell, B. W., Gertler, F. B., & Cooper, J. A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.1.121 · Cited by 339 · see citing works
Sokka, A.-L., Putkonen, N., Mudò, G., Pryazhnikov, E., Reijonen, S., Khiroug, L. S., Belluardo, N., Lindholm, D., & Korhonen, L. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4289-06.2007 · Cited by 311 · see citing works
Self-citationReelin signaling is impaired in autism
Fatemi, S. H., Snow, A. V., Stary, J. M., Araghi-Niknam, M., Reutiman, T. J., Lee, S., Brooks, A. I., & Pearce, D. A. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.12.018 · Cited by 280 · see citing works
The Reelin signaling pathway promotes dendritic spine development in hippocampal neurons
Niu, S., Yabut, O., & D'Arcangelo, G. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1917-08.2008 · Cited by 266 · see citing works
A mechanism for inside-out lamination in the neocortex
Cooper, J. A. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2007.12.003 · Cited by 236 · see citing works
Berzaghi, M. D. P., Cooper, J. D., Ċastrén, E., Zafra, F., Sofroniew, M. V., Thoenen, H., & Lindholm, D. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-09-03818.1993 · Cited by 206 · see citing works
Self-citationReelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density
Rogers, J. T., Rusiana, I., Trotter, J., Zhao, L., Donaldson, E., Pak, D. T. S., Babus, L. W., Peters, M., Banko, J. L., Chavis, P., et al. (2011) · Learning & Memory · doi:10.1101/lm.2153511 · Cited by 181 · see citing works
Lindholm, D., Carroll, P., Tzimagiorgis, G., & Thoenen, H. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01607.x · Cited by 180 · see citing works
Self-citationBDNF Regulates Reelin Expression and Cajal-Retzius Cell Development in the Cerebral Cortex
Ringstedt, T., Linnarsson, S., Wagner, J., Lendahl, U., Kokaia, Z., Arenas, E., Ernfors, P., & Ibáñez, C. F. (1998) · Neuron · doi:10.1016/s0896-6273(00)80540-1 · Cited by 161 · see citing works
Marty, S., Carroll, P., Cellerino, A., Ċastrén, E., Staiger, V., Thoenen, H., & Lindholm, D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00675.1996 · Cited by 157 · see citing works
Self-citationReelin signaling antagonizes β-amyloid at the synapse
Durakoglugil, M. S., Chen, Y., White, C. L., Kavalali, E. T., & Herz, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908176106 · Cited by 153 · see citing works
Hong, C., Duit, S., Jalonen, P., Out, R., Scheer, L., Sorrentino, V., Boyadjian, R., Rodenburg, K. W., Foley, E., Korhonen, L., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.123729 · Cited by 142 · see citing works
Self-citationEmerging topics in Reelin function
Förster, E., Bock, H. H., Herz, J., Chai, X., Frotscher, M., & Zhao, S. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07222.x · Cited by 130 · see citing works
Hyrskyluoto, A., Pulli, I., Törnqvist, K., Ho, T. H., Korhonen, L., & Lindholm, D. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.170 · Cited by 122 · see citing works
Self-citationReelin Signaling Facilitates Maturation of CA1 Glutamatergic Synapses
Qiu, S., & Weeber, E. J. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00869.2006 · Cited by 115 · see citing works
Scotti, E., Calamai, M., Goulbourne, C. N., Zhang, L., Hong, C., Lin, R. R., Choi, J., Pilch, P. F., Fong, L. G., Zou, P., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01716-12 · Cited by 80 · see citing works
Olsson, P.-A., Korhonen, L., Mercer, E. A., & Lindholm, D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.51.36288 · Cited by 77 · see citing works
Self-citationDuit, S., Mayer, H., Blake, S. M., Schneider, W. J., & Nimpf, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025973 · Cited by 71 · see citing works
Thi, H., Tselykh, T. V., Mäkelä, J., Ho, T. H., Olkkonen, V. M., Bornhauser, B. C., Korhonen, L., Zelcer, N., & Lindholm, D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.341248 · Cited by 67 · see citing works
Self-citationKorhonen, L., Belluardo, N., & Lindholm, D. (2001) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0935 · Cited by 67 · see citing works
Self-citationBornhauser, B. C., Olsson, P., & Lindholm, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306271200 · Cited by 66 · see citing works
Self-citationKairisalo, M., Korhonen, L., Sepp, M., Pruunsild, P., Kukkonen, J. P., Kivinen, J., Timmusk, T., Blomgren, K., & Lindholm, D. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06898.x · Cited by 65 · see citing works
Self-citationReelin-Disabled-1 signaling in neuronal migration: splicing takes the stage
Gao, Z., & Godbout, R. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1171-6 · Cited by 50 · see citing works
Putkonen, N., Kukkonen, J. P., Mudò, G., Putula, J., Belluardo, N., Lindholm, D., & Korhonen, L. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07858.x · Cited by 30 · see citing works
Self-citationBornhauser, B. C., Johansson, C., & Lindholm, D. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01010-x · Cited by 24 · see citing works
Self-citationKreuter, R., Soutar, A. K., & Wade, D. P. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32441-x · Cited by 19 · see citing works
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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)
- PMC
- PMC3795259
- OpenAlex
- W2138367192
- Semantic Scholar
- b21271d6183a47be88c5a36ecd8284073231fe49
- 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
- hybrid
- doi.org
- Licence
- 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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