A lysophospholipid acyltransferase antagonist, CI-976, creates novel membrane tubules marked by intracellular phospholipase A1 KIAA0725p
A lysophospholipid acyltransferase antagonist, CI-976, creates novel membrane tubules marked by intracellular phospholipase A1 KIAA0725p
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DOI：
10.1007/s11010-013-1563-4
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发表时间：
2013-04-01
影响因子：
4.3
通讯作者：
Tani, Katsuko
中科院分区：
文献类型：
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作者：
Baba, Takashi;Yamamoto, Akitsugu;Tani, Katsuko
CI-976是一种溶血磷脂酰基转移酶拮抗剂，已知其可能通过增加膜中溶血磷脂含量来影响分泌和内吞膜运输途径。我们以前的研究表明，通过细胞内磷脂酶A（1）KIAA 0725 p（也称为DDHD 2和iPLA（1）γ）的作用形成的溶血磷脂可能对这种酶与膜的结合很重要。在这项研究中，我们检查了CI-976对KIAA 0725 p的膜结合的影响。在HeLa细胞中，KIAA 0725 p定位于高尔基体和胞质溶胶中，而在小鼠胚胎成纤维细胞（MEF）中，发现其主要定位于胞质溶胶中，其中一些定位于包括顺式高尔基体的后内质网隔室上。用CI-976处理MEFs诱导KIAA 0725 p重新分布到膜小管，其邻近破碎的线粒体。这些小管没有典型的细胞器标记，包括高尔基体蛋白质装饰。一个人KIAA 0725 p突变体，表现出降低的膜结合能力，也重新分配到膜结构后CI-976处理。我们的数据表明，KIAA 0725 p与膜的关联受脂质代谢的调节，CI-976可能会产生独特的膜结构，可以被KIAA 0725 p标记。
CI-976 is a lysophospholipid acyltransferase antagonist that is known to affect secretory and endocytic membrane-trafficking pathways likely by increasing the lysophospholipid content in membranes. Our previous study suggested that lysophospholipids formed through the action of an intracellular phospholipase A(1), KIAA0725p (also known as DDHD2 and iPLA(1)gamma), may be important for the association of this enzyme with membranes. In this study, we examined the effect of CI-976 on the membrane association of KIAA0725p. While in HeLa cells KIAA0725p is localized in the Golgi and cytosol, in mouse embryonic fibroblasts (MEFs), it was found to be principally localized in the cytosol with some on post-endoplasmic reticulum compartments including the cis-Golgi. Treatment of MEFs with CI-976 induced the redistribution of KIAA0725p to membrane tubules, which were in vicinity to fragmented mitochondria. These tubules were not decorated with canonical organelle markers including Golgi proteins. A human KIAA0725p mutant, which exhibits decreased membrane-binding ability, was also redistributed to membrane structures upon CI-976 treatment. Our data suggest that the association of KIAA0725p with membranes is regulated by lipid metabolism, and that CI-976 may create unique membrane structures that can be marked by KIAA0725p.