Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Biol. Chem. 277 (1): 303-309

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Reelin Is a Serine Protease of the Extracellular Matrix*

Carlo C. Quattrocchiabc, Francesca Wannenesde, Antonio M. Persicoa, Silvia Anna Ciafréd, Gabriella D'Arcangelofghi, Maria G. Faracef, and Flavio Kelleraj

From the a Laboratory of Neuroscience, Department of Physiology and Neuroscience, Università "Campus Bio-Medico," Via Longoni 83, 00155 Roma, Italy, the b Program in Neuroscience, Faculty of Medicine, University of Brescia, Via Valsabbina 19, 25123 Brescia, Italy, the d Department of Experimental Medicine and Biochemical Sciences, Università di Tor Vergata, Via di Tor Vergata 135, 00133 Roma, Italy, the e Department of Internal Medicine, Università di Tor Vergata, Via di Tor Vergata 135, 00133 Roma, Italy, and f The Cain Foundation Laboratories, g Department of Pediatrics, h Program in Developmental Biology and i Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030

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.


* This work was supported by Consiglio Nazionale delle Ricerche Programma "Biomolecole per la salute umana" Grant 99.00555.PF33.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

c Present address: Dept. of Pediatrics-Neurology, Baylor College of Medicine, 1102 Bates St., MC 3-6365, Houston, TX 77030.

j To whom correspondence should be addressed: Laboratory of Neuroscience, Università "Campus Bio-Medico," Via Longoni 83, 00155 Roma, Italy. Tel.: 39-06-2254-1335; Fax: 39-06-22-54-14-56; E-mail: f.keller@unicampus.it.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A transcriptome signature of endothelial lymphatic cells coexists with the chronic oxidative stress signature in radiation-induced post-radiotherapy breast angiosarcomas.
N.-S. Hadj-Hamou, M. Lae, A. Almeida, d. l. Grange P, Y. Kirova, X. Sastre-Garau, and B. Malfoy (2012)
Carcinogenesis
   Abstract »    Full Text »    PDF »
Go or Stop? Divergent Roles of Reelin in Radial Neuronal Migration.
S. Zhao and M. Frotscher (2010)
Neuroscientist 16, 421-434
   Abstract »    PDF »
Cellular Form of Prion Protein Inhibits Reelin-Mediated Shedding of Caspr from the Neuronal Cell Surface to Potentiate Caspr-Mediated Inhibition of Neurite Outgrowth.
V. Devanathan, I. Jakovcevski, A. Santuccione, S. Li, H. J. Lee, E. Peles, I. Leshchyns'ka, V. Sytnyk, and M. Schachner (2010)
J. Neurosci. 30, 9292-9305
   Abstract »    Full Text »    PDF »
The genetic and molecular bases of monogenic disorders affecting proteolytic systems.
I Richard (2005)
J. Med. Genet. 42, 529-539
   Abstract »    Full Text »    PDF »
Environmental Control of the Survival and Differentiation of Dentate Granule Neurons.
J.-A. Kim, R. Koyama, R. X. Yamada, M. K. Yamada, N. Nishiyama, N. Matsuki, and Y. Ikegaya (2004)
Cereb Cortex 14, 1358-1364
   Abstract »    Full Text »    PDF »
Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.
C. Erbel-Sieler, C. Dudley, Y. Zhou, X. Wu, S. J. Estill, T. Han, R. Diaz-Arrastia, E. W. Brunskill, S. S. Potter, and S. L. McKnight (2004)
PNAS 101, 13648-13653
   Abstract »    Full Text »    PDF »
Response to Comment on "Reelin Promotes Peripheral Synapse Elimination and Maturation".
G. D'Arcangelo (2004)
Science 303, 1977c
   Full Text »    PDF »
Is Reelin the Answer to Synapse Elimination at the Neuromuscular Junction?.
B. Chih and P. Scheiffele (2003)
Sci. STKE 2003, pe45
   Abstract »    Full Text »    PDF »
Extracellular proteases and their inhibitors ingenetic diseases of the central nervous system.
F. Molinari, V. Meskanaite, A. Munnich, P. Sonderegger, and L. Colleaux (2003)
Hum. Mol. Genet. 12, R195-R200
   Abstract »    Full Text »    PDF »
Reelin Promotes Peripheral Synapse Elimination and Maturation.
C. C. Quattrocchi, C. Huang, S. Niu, M. Sheldon, D. Benhayon, J. Cartwright Jr., D. R. Mosier, F. Keller, and G. D'Arcangelo (2003)
Science 301, 649-653
   Abstract »    Full Text »    PDF »
A reelin-integrin receptor interaction regulates Arc mRNA translation in synaptoneurosomes.
E. Dong, H. Caruncho, W. S. Liu, N. R. Smalheiser, D. R. Grayson, E. Costa, and A. Guidotti (2003)
PNAS 100, 5479-5484
   Abstract »    Full Text »    PDF »
Teneurin 2 is expressed by the neurons of the thalamofugal visual system in situ and promotes homophilic cell-cell adhesion in vitro.
B. P. Rubin, R. P. Tucker, M. Brown-Luedi, D. Martin, and R. Chiquet-Ehrismann (2003)
Development 129, 4697-4705
   Abstract »    Full Text »    PDF »
Role of Integrins in the Development of the Cerebral Cortex.
R. S. Schmid and E.S. Anton (2003)
Cereb Cortex 13, 219-224
   Abstract »    Full Text »    PDF »
Reelin Immunoreactivity in the Adult Primate Brain: Intracellular Localization in Projecting and Local Circuit Neurons of the Cerebral Cortex, Hippocampus and Subcortical Regions.
V. Martinez-Cerdeno, M. J. Galazo, C. Cavada, and F. Clasca (2002)
Cereb Cortex 12, 1298-1311
   Abstract »    Full Text »    PDF »
The Structure of Human Prokallikrein 6 Reveals a Novel Activation Mechanism for the Kallikrein Family.
F. X. Gomis-Ruth, A. Bayes, G. Sotiropoulou, G. Pampalakis, T. Tsetsenis, V. Villegas, F. X. Aviles, and M. Coll (2002)
J. Biol. Chem. 277, 27273-27281
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882