Monounsaturated fatty acid modification of Wnt protein: Its role in Wnt secretion
Monounsaturated fatty acid modification of Wnt protein: Its role in Wnt secretion
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DOI：
10.1016/j.devcel.2006.10.003
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发表时间：
2006-12-01
影响因子：
11.8
通讯作者：
Takada, Shinji
中科院分区：
文献类型：
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作者：
Takada, Ritsuko;Satomi, Yoshinori;Takada, Shinji
Wnt蛋白的分泌和细胞外转运被认为是一个受良好调控的过程。已知Wnt在保守的半胱氨酸残基（鼠Wnt-3a中的Cys 77）处被棕榈酸酰化，并且该残基似乎是控制细胞外转运所需的。在这里，我们表明，小鼠Wnt-3a也酰化在一个保守的丝氨酸残基（Ser 209）。值得注意的是，我们证明了这个残基被单不饱和脂肪酸棕榈油酸修饰。在Ser 209处酰化缺陷的Wnt-3a不从培养的细胞或爪蟾胚胎中分泌，但其保留在内质网（ER）中。此外，豪猪，一种与膜结合的O-酰基转移酶结构相似的蛋白质，需要Ser 209依赖性酰化，以及Wnt-3a从ER运输分泌。这些结果强烈表明，Wnt蛋白需要一个特定的脂质修饰，在分泌过程中适当的细胞内运输。
The secretion and extracellular transport of Wnt protein are thought to be well-regulated processes. Wnt is known to be acylated with palmitic acid at a conserved cysteine residue (Cys77 in murine Wnt-3a), and this residue appears to be required for the control of extracellular transport. Here, we show that murine Wnt-3a is also acylated at a conserved serine residue (Ser209). Of note, we demonstrated that this residue is modified with a monounsaturated fatty acid, palmitoleic acid. Wnt-3a defective in acylation at Ser209 is not secreted from cells in culture or in Xenopus embryos, but it is retained in the endoplasmic reticulum (ER). Furthermore, Porcupine, a protein with structural similarities to membrane-bound O-acyltransferases, is required for Ser209-dependent acylation, as well as for Wnt-3a transport from the ER for secretion. These results strongly suggest that Wnt protein requires a particular lipid modification for proper intracellular transport during the secretory process.