title: Reelin is a serine protease of the extracellular matrix.
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.
authors.affiliation: Laboratory of Neuroscience, Department of Physiology and Neuroscience, Università Campus Bio-Medico, Via Longoni 83, 00155 Roma, Italy.
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Quattrocchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Wannenes
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Persico
authors.forename: Silvia Anna
authors.initials: SA
authors.lastname: Ciafré
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Arcangelo
authors.forename: Maria G
authors.initials: MG
authors.lastname: Farace
authors.forename: Flavio
authors.initials: F
authors.lastname: Keller
mesh_terms: D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000502:physiology; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D016023:Integrins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases