Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
FEBS Lett. 2012 Sep 21;586(19):3349-53. doi: 10.1016/j.febslet.2012.07.017. Epub 2012 Jul 20.
Reelin is a glycoprotein essential for brain development and functions. Reelin is subject to specific proteolysis at two distinct (N-t and C-t) sites, and these cleavages significantly diminish Reelin activity. The decrease of Reelin activity is detrimental for brain function, but the protease that catalyzes specific cleavage of Reelin remains elusive. Here we found that a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) cleaves Reelin in an isoform-specific manner. Among ADAMTS-4 isoforms, p50 cleaves the N-t site only, while p75 cleaves both sites. This is the first report identifying a protease that can specifically cleave Reelin.
Reelin 是一种对大脑发育和功能至关重要的糖蛋白。 Reelin 在两个独特的（N 端和 C 端）位点受到特定的蛋白水解，这些切割显著降低了 Reelin 的活性。 Reelin 活性的降低对大脑功能有害，但催化 Reelin 特异性切割的蛋白酶仍未被发现。在这里，我们发现一种带有血小板反应蛋白基序的解整合素和金属蛋白酶 4（ADAMTS-4）以同工型特异性的方式切割 Reelin。在 ADAMTS-4 同工型中，p50 仅切割 N 端位点，而 p75 切割两个位点。这是首次报道鉴定出一种能够特异性切割 Reelin 的蛋白酶。
