Reelin is a serine protease of the extracellular matrix

Carlo C. Quattrocchi, Francesca Wannenes, Antonio M. Persico, Silvia Anna Ciafré, Gabriella D'Arcangelo, Maria G. Farace, Flavio Keller

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)303-309
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number1
DOIs
Publication statusPublished - Jan 4 2002

ASJC Scopus subject areas

  • Biochemistry

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    Quattrocchi, C. C., Wannenes, F., Persico, A. M., Ciafré, S. A., D'Arcangelo, G., Farace, M. G., & Keller, F. (2002). Reelin is a serine protease of the extracellular matrix. Journal of Biological Chemistry, 277(1), 303-309. https://doi.org/10.1074/jbc.M106996200