A disintegrin and metalloproteinase with thrombospondin motifs 2 cleaves and inactivates Reelin in the postnatal cerebral cortex and hippocampus, but not in the cerebellum

Publication date: Available online 3 September 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Yuko Yamakage, Michinao Kato, Aya Hongo, Himari Ogino, Keisuke Ishii, Takumi Ishizuka, Takana Kamei, Hitomi Tsuiji, Tomomi Miyamoto, Hisashi Oishi, Takao Kohno, Mitsuharu HattoriAbstractReelin plays important roles in regulating neuronal development, modulating synaptic function, and counteracting amyloid β toxicity. A specific proteolytic cleavage (N-t cleavage) of Reelin abolishes its biological activity. We recently identified ADAMTS-3 (a disintegrin and metalloproteinase with thrombospondin motifs 3) as the major N-t cleavage enzyme in the embryonic and early postnatal brain. The contribution of other proteases, particularly in the postnatal brain, has not been demonstrated in vivo.ADAMTS-2, -3 and -14 share similar domain structures and substrate specificity, raising the possibility that ADAMTS-2 and -14 may cleave Reelin. We found that recombinant ADAMTS-2 protein expressed in cultured cell lines cleaves Reelin at the N-t site as efficiently as ADAMTS-3 while recombinant ADAMTS-14 hardly cleaves Reelin. The disintegrin domain is necessary for the Reelin-cleaving activity of ADAMTS-2 and -3. ADAMTS-2 is expressed in the adult brain at approximately the same level as ADAMTS-3. We generated ADAMTS-2 knockout (KO) mice and found that ADAMTS-2 significantly contributes to the N-t cleavage and inactivation of Reelin in the postnatal cerebral cortex and hippocampus, but mu...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research