Reelin is a serine protease of the extracellular matrix.
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.
Quattrocchi
Carlo C
CC
Laboratory of Neuroscience, Department of Physiology and Neuroscience, Università Campus Bio-Medico, Via Longoni 83, 00155 Roma, Italy.
Wannenes
Francesca
F
Persico
Antonio M
AM
Ciafré
Silvia Anna
SA
D'Arcangelo
Gabriella
G
Farace
Maria G
MG
Keller
Flavio
F
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*
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