Proteins of the CNR Family Are Multiple Receptors for Reelin
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Layering and positioning of neurons require Reelin- and Src family-associated mammalian Disabled (mDab1). Cadherin-related neuronal receptor (CNR) genes are expressed in neurons of the cortical layer, but not in Cajal-Retzius cells expressing Reelin. This leads us to hypothesize that CNRs bound to Fyn of the Src family are receptors for Reelin. Herein we confirm the association and colocalization of CNR proteins with Reelin. This binding is blocked by CR-50 antibody against Reelin, as well as by monoclonal antibodies produced against CNRs. Both disturb the signaling pathway from Reelin to mDab1 and the positioning of cortical neurons in vitro. These results strongly suggest that the CNR family proteins are multiple Reelin receptors. In addition, differential conservation of the Reelin-binding domain among terrestrial vertebrates may be pertinent to the diversity or complexity of brains.
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Dab1 phosphorylation is essential in Reelin signaling.
“Because the Dab1 phosphorylation is essential in Reelin signaling (24, 35–37)”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [37]
Lipoprotein receptors (VLDLR and ApoER2) and CNR family members bind to full-length Reelin.
“Recently, lipoprotein receptors (VLDLR and ApoER2) and the CNR family members were reported to bind to the full-length Reelin (35–37).”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [37]
CNR proteins bind to the subrepeat B of the first Reelin repeat, which is downstream of the CR-50 epitope region.
“the CNR proteins bind to the subrepeat B of the first Reelin repeat, which is downstream of the CR-50 epitope region (37).”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [37]
CR-50 antibody inhibited Reelin binding to VLDLR-expressing 293T cells and to the extracellular domain of CNR1 protein.
“CR-50 antibody inhibited Reelin binding to VLDLR-expressing 293T cells (35) and to the extracellular domain of CNR1 protein (37).”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [37]
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- Authors
- Senzaki, K., Ogawa, M., & Yagi, T.
- Affiliations
- National Institute for Physiological Sciences (JP)
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Yagi, Takeshi
- ORCID
- Yagi, Takeshi
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 99
- Issue
- 6
- Pages
- 635-647
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2056281513
- Cited by
- 272
- References
- 45
- Citations by year
- 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 6 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 2
- FWCI
- 14.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Japan Science and Technology Corporation
- Ministry of Education, Culture, Sports, Science and Technology
- 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
- reelin, Reelin receptors, Fyn, Src family kinases, protein colocalization, brain evolution
- MeSH terms
- Reelin Protein, Protocadherins, Animals, Cells, Cultured, Cerebral Cortex, Humans, Mice, Inbred Strains, Nerve Tissue Proteins, Neurons, Neuropeptides, Protein Binding, Rats, Inbred F344, Receptors, Cell Surface, Sensory Receptor Cells, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Cadherins, Extracellular Matrix Proteins, In Situ Hybridization, Protein Structure, Tertiary, Evolution, Molecular, Mice, Rats
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