Cited by 154Axon Guidance and Neuronal SignalingProtease and Inhibitor MechanismsNeurogenesis and neuroplasticity mechanisms

Reelin Is a Serine Protease of the Extracellular Matrix

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Quattrocchi, Carlo C., Wannenes, Francesca, Persico, Antonio M., Ciafré, Silvia Anna, D'Arcangelo, Gabriella, Farace, Maria G., Keller, Flavio·2002·Journal of Biological Chemistry

Abstract

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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Crossref · 10.1074/jbc.m106996200

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  • Reelin regulates neuronal lamination during embryonic development and supports neuronal migration and synaptic plasticity throughout life.

    “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].”

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  1. [10]10. Pesold, C., Liu, W. S., Guidotti, A., Costa, E. & Caruncho, H. J. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 3217-3222
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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
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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