|
|
© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
Reelin Is a Serine Protease of the Extracellular Matrix*
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.
The editors suggest the following Related Resources on Science sites:In Science Signaling
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
|
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882
News | Science Journals | Careers | Blogs and Communities | Multimedia | Collections | Help | Site Map | RSS
Subscribe | Feedback | Privacy / Legal | About Us | Advertise With Us | Contact Us
© 2002 American Association for the Advancement of Science. All Rights Reserved.
AAAS is a partner of HINARI, AGORA, OARE, PatientInform, CrossRef, and COUNTER.
You have reached the bottom of the page. Back to top