The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity
The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity
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DOI：
10.1242/jcs.163063
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发表时间：
2015-03-15
影响因子：
4
通讯作者：
Alfandari, Dominique
中科院分区：
文献类型：
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作者：
Abbruzzese, Genevieve;Gorny, Anne-Kathrin;Alfandari, Dominique
颅神经嵴细胞（CNC）是一种瞬时干细胞群，起源于神经板和表皮的边界，并向腹侧迁移，有助于大多数面部结构，包括骨骼，软骨，肌肉和神经节。ADAM13是一种细胞表面金属蛋白酶，对CNC细胞迁移至关重要。本研究表明，在非洲爪蟾胚胎中，Wnt受体Fz4与ADAM13富含半胱氨酸的结构域结合，并在体内负调控其蛋白水解活性。Fz4功能的增加可以抑制CNC细胞的迁移，并且可以通过ADAM13功能的增加来挽救。Fz4功能的丧失也会抑制CNC细胞迁移并诱导成熟ADAM13的减少，同时ADAM13细胞质片段的增加，ADAM13细胞质片段已知会转运到细胞核中以调节基因表达。我们认为Fz4在ADAM13转运到质膜的过程中与ADAM13结合以调节其蛋白水解活性。
Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity.