Reelin, the extracellular matrix protein deficient in reeler mutant mice, is processed by a metalloproteinase.
Reelin is the extracellular protein defective in reeler mice. It is believed that reelin acts via the extracellular matrix to influence the development of nearby neurons, but the mechanism remains thus far unknown. In the present work, we present in vivo and in vitro evidence that reelin is cleaved. This processing did not occur in Relnrl-Orl mutant mice in which reelin is not secreted and was prevented in explant cultures by brefeldin treatment, suggesting that it takes place extracellularly or in a postendoplasmic reticulum compartment. Reelin cleavage was inhibited by zinc chelators known to inhibit metalloproteinases but was unaffected by inhibitors of serine, cysteine, or aspartate proteinases. Furthermore, reelin cleavage was insensitive to inhibitors of matrixins, neprilysin, meprin, and peptidyl dipeptidase A, suggesting that the processing enzyme belongs to a different enzyme family. This enzyme and the physiological meaning of reelin processing remain to be characterized further.
Lambert de Rouvroit
C
C
Neurobiology Unit, University of Namur Medical School, 61 rue de Bruxelles, B-5000 Namur, Belgium.
de Bergeyck
V
V
Cortvrindt
C
C
Bar
I
I
Eeckhout
Y
Y
Goffinet
A M
AM
D000818:Animals; D001921:Brain / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D046508:Culture Techniques; D004622:Embryo, Mammalian; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000172:deficiency; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000172:deficiency; D011233:Precipitin Tests; D011480:Protease Inhibitors / Q000494:pharmacology; D000091042:Reelin Protein; D012697:Serine Endopeptidases
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D011480:Protease Inhibitors; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases