Ypk1, the yeast orthologue of the human serum- and glucocorticoid-induced kinase, is required for efficient uptake of fatty acids
Ypk1, the yeast orthologue of the human serum- and glucocorticoid-induced kinase, is required for efficient uptake of fatty acids
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DOI：
10.1242/jcs.063073
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发表时间：
2010-07-01
影响因子：
4
通讯作者：
Schneiter, Roger
中科院分区：
文献类型：
--
作者：
Jacquier, Nicolas;Schneiter, Roger
脂肪酸是各种组织的重要能量来源。然而，调节和控制从循环中摄取游离脂肪酸的机制知之甚少。在这里，我们表明，酵母细胞有效的脂肪酸摄取需要蛋白激酶Ypk 1，人血清和糖皮质激素诱导的激酶Sgk 1的直向同源物。ypk 1 δ突变体细胞在使细胞对脂肪酸营养缺陷的条件下不能生长，显示出放射性标记或荧光标记的脂肪酸的摄取减少，缺乏摄取活性的促进组分，并且在牛血清白蛋白（BSA）反萃取隔室中具有升高的脂肪酸水平。有效的脂肪酸摄取和/或掺入需要YPK 1的蛋白激酶活性，因为YPK 1的激酶死点突变等位基因在该过程中是有缺陷的。Ypk 1在脂肪酸摄取和/或掺入中的这种功能在功能上是保守的，因为人Sgk 1激酶的表达拯救了ypk 1 Delta突变酵母。这些观察结果表明，YPK 1和可能的人Sgk 1激酶影响脂肪酸摄取，从而通过调节内吞作用的能量稳态。与这一主张相一致的是，阻断内吞作用早期步骤的突变显示脂肪酸摄取水平降低。
Fatty acids constitute an important energy source for various tissues. The mechanisms that mediate and control uptake of free fatty acids from the circulation, however, are poorly understood. Here we show that efficient fatty-acid uptake by yeast cells requires the protein kinase Ypk1, the orthologue of the human serum-and glucocorticoid-induced kinase Sgk1. ypk1 Delta mutant cells fail to grow under conditions that render cells auxotrophic for fatty acids, show a reduced uptake of radiolabelled or fluorescently labelled fatty acids, lack the facilitated component of the uptake activity, and have elevated levels of fatty acids in a bovine serum albumin (BSA) back-extractable compartment. Efficient fatty-acid uptake and/or incorporation requires the protein-kinase activity of Ypk1, because a kinase-dead point-mutant allele of YPK1 is defective in this process. This function of Ypk1 in fatty-acid uptake and/or incorporation is functionally conserved, because expression of the human Sgk1 kinase rescues ypk1 Delta mutant yeast. These observations suggest that Ypk1 and possibly the human Sgk1 kinase affect fatty-acid uptake and thus energy homeostasis through regulating endocytosis. Consistent with such a proposition, mutations that block early steps of endocytosis display reduced levels of fatty-acid uptake.