More Favorable Palmitic Acid Over Palmitoleic Acid Modification of Wnt3 Ensures Its Localization and Activity in Plasma Membrane Domains
More Favorable Palmitic Acid Over Palmitoleic Acid Modification of Wnt3 Ensures Its Localization and Activity in Plasma Membrane Domains
复制标题
DOI：
10.3389/fcell.2019.00281
复制
发表时间：
2019-11-15
影响因子：
5.5
通讯作者：
Ozhan, Gunes
中科院分区：
文献类型：
--
作者：
Azbazdar, Yagmur;Ozalp, Ozgun;Ozhan, Gunes
虽然质膜成分的横向组织已被证明可以控制Wnt配体优先在有序的膜结构域中与其受体的结合，但Wnt的翻译后脂质修饰对这种选择性结合的作用尚不清楚。在这里，我们确定，典型的Wnt大概是酰化棕榈酸，饱和的16碳脂肪酸，在一个保守的丝氨酸残基。Wnt 3的酰化对于其分泌和与Fz 8结合是必需的，而它对于Wnt 3在有序膜结构域中的适当结合和结构域样扩散是必需的。我们进一步揭示了非棕榈酰化Wnt 3不能激活斑马鱼胚胎或哺乳动物细胞中的Wnt/β-连环蛋白信号。基于这些结果，我们提出，典型的Wnt的脂质化，大概是由饱和脂肪酸，确定其在与质膜的适当域中的受体相互作用的能力，最终保持信号传导活性的控制。
While the lateral organization of plasma membrane components has been shown to control binding of Wnt ligands to their receptors preferentially in the ordered membrane domains, the role of posttranslational lipid modification of Wnt on this selective binding is unknown. Here, we identify that the canonical Wnt is presumably acylated by palmitic acid, a saturated 16-carbon fatty acid, at a conserved serine residue. Acylation of Wnt3 is dispensable for its secretion and binding to Fz8 while it is essential for Wnt3's proper binding and domain-like diffusion in the ordered membrane domains. We further unravel that non-palmitoylated Wnt3 is unable to activate Wnt/beta-catenin signaling either in zebrafish embryos or in mammalian cells. Based on these results, we propose that the lipidation of canonical Wnt, presumably by a saturated fatty acid, determines its competence in interacting with the receptors in the appropriate domains of the plasma membrane, ultimately keeping the signaling activity under control.