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Reelin Is a Serine Protease of the Extracellular Matrix
Open accessAbstract
Reelin is an extracellular matrix protein that plays a pivotal role in development of the central nervous system. Reelin is also expressed in the adult brain, notably in the cerebral cortex, where it might play a role in synaptic plasticity. The mechanism of action of reelin at the molecular level has been the subject of several hypotheses. Here we show that reelin is a serine protease and that proteolytic activity is relevant to its function, since (i) Reelin expression in HEK 293T cells impairs their ability to adhere to fibronectin-coated surfaces, and adhesion to fibronectin is restored by micromolar concentrations of diisopropyl phosphorofluoridate, a serine hydrolase inhibitor; (ii) purified Reelin binds FP-Peg-biotin, a trap probe which irreversibly binds to serine residues located in active catalytic sites of serine hydrolases; (iii) purified Reelin rapidly degrades fibronectin and laminin, while collagen IV is degraded at a much slower rate; fibronectin degradation is inhibited by inhibitors of serine proteases, and by monoclonal antibody CR-50, an antibody known to block the function of Reelin both in vitro and in vivo. The proteolytic activity of Reelin on adhesion molecules of the extracellular matrix and/or receptors on neurons may explain how Reelin regulates neuronal migration and synaptic plasticity.
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“As a serine protease of the extracellular matrix, Reelin regulates proper lamination of neurons during embryonic development and helps in migration of neurons and maintenance of synaptic plasticity throughout life [135–137].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [135]
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Metadata
- Authors
- Quattrocchi, C. C., Wannenes, F., Persico, A. M., Ciafré, S. A., D'Arcangelo, G., Farace, M. G., & Keller, F.
- Affiliations
- Università Campus Bio-Medico (IT)
- University of Rome Tor Vergata (IT)
- Baylor College of Medicine (US)
- Corresponding author
- Keller, Flavio
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 277
- Issue
- 1
- Pages
- 303-309
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1971016056
- Cited by
- 154
- References
- 41
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 9
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- reelin, serine protease activity, extracellular matrix, fibronectin degradation, laminin degradation, type IV collagen, cell adhesion, serine hydrolase inhibitors, diisopropylfluorophosphate, neuronal migration, synaptic plasticity, central nervous system development
- MeSH terms
- Reelin Protein, Cell Adhesion, Cells, Cultured, Humans, Nerve Tissue Proteins, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Integrins, Extracellular Matrix Proteins
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