The Rim101 pathway is involved in Rsb1 expression induced by altered lipid asymmetry
The Rim101 pathway is involved in Rsb1 expression induced by altered lipid asymmetry
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DOI：
10.1091/mbc.e07-08-0806
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发表时间：
2008-05-01
影响因子：
3.3
通讯作者：
Igarashi, Yasuyuki
中科院分区：
文献类型：
--
作者：
Ikeda, Mika;Kihara, Akio;Igarashi, Yasuyuki
生物膜由脂质双层组成。质膜的两个小叶之间的脂质组成不同，产生脂质不对称。适当的脂质不对称性的维持在生理上是相当重要的，并且其崩溃诱导几种细胞反应，包括细胞凋亡和血小板凝固。因此，必须恢复脂质不对称性的变化以维持“脂质不对称性稳态”。然而，迄今为止，还没有发现脂质不对称传感蛋白或任何相关的下游信号通路。我们最近证明，表达的假定酵母鞘氨醇长链碱基转运蛋白/转位酶Rsb 1的诱导时，甘油磷脂的不对称性被改变。使用突变体筛选，我们确定了pH响应Rim 101通路，蛋白激酶Mck 1，和转录因子Mot 3都在脂质不对称信号中起作用，并且Rim 101通路响应于脂质不对称的变化而被激活。激活的转录因子Rim 101通过抑制另一个转录抑制因子Nrg 1诱导Rsb 1表达。脂质不对称性的变化伴随着细胞表面暴露的带负电荷的磷脂，我们推测，Rim 101途径识别的表面电荷。
Biological membranes consist of lipid bilayers. The lipid compositions between the two leaflets of the plasma membrane differ, generating lipid asymmetry. Maintenance of proper lipid asymmetry is physiologically quite important, and its collapse induces several cellular responses including apoptosis and platelet coagulation. Thus, a change in lipid asymmetry must be restored to maintain "lipid asymmetry homeostasis." However, to date no lipid asymmetry-sensing proteins or any related downstream signaling pathways have been identified. We recently demonstrated that expression of the putative yeast sphingoid long-chain base transporter/translocase Rsb1 is induced when glycerophospholipid asymmetry is altered. Using mutant screening, we determined that the pH-responsive Rim101 pathway, the protein kinase Mck1, and the transcription factor Mot3 all act in lipid asymmetry signaling, and that the Rim101 pathway was activated in response to a change in lipid asymmetry. The activated transcription factor Rim101 induces Rsb1 expression via repression of another transcription repressor, Nrg1. Changes in lipid asymmetry are accompanied by cell surface exposure of negatively charged phospholipids; we speculate that the Rim101 pathway recognizes the surface charges.