Reelin Is a Serine Protease of the Extracellular Matrix

• Published in: The Journal of biological chemistry Vol. 277; no. 1; pp. 303 - 309
• Main Authors: Quattrocchi, Carlo C., Wannenes, Francesca, Persico, Antonio M., Ciafré, Silvia Anna, D'Arcangelo, Gabriella, Farace, Maria G., Keller, Flavio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.01.2002; American Society for Biochemistry and Molecular Biology
• Subjects: Cell Adhesion; Cell Adhesion Molecules, Neuronal - chemistry; Cell Adhesion Molecules, Neuronal - isolation & purification; Cell Adhesion Molecules, Neuronal - metabolism; Cells, Cultured; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - isolation & purification; Extracellular Matrix Proteins - metabolism; Humans; Integrins - physiology; Nerve Tissue Proteins; Serine Endopeptidases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M106996200

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 bothin 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.