Phospholipase D2 is required for efficient endocytic recycling of transferrin receptors.
Phospholipase D2 is required for efficient endocytic recycling of transferrin receptors.
复制标题
转铁蛋白受体的有效内吞再循环需要磷脂酶 D2。
DOI：
10.1091/mbc.e05-05-0389
复制
发表时间：
2006
影响因子：
3.3
通讯作者：
Roth,MichaelG
中科院分区：
文献类型：
--
作者：
Padrón,David;Tall,ReneeD;Roth,MichaelG
RNA 干扰介导的磷脂酶 D2 (PLD2) 消耗（而非 PLD1）抑制 HeLa 细胞中转铁蛋白受体的循环，而内化率不受任一 PLD 消耗的影响。尽管两种 PLD 同工型的减少都会抑制佛波醇 12-肉豆蔻酸 13-乙酸酯刺激的 PLD 活性，但只有 PLD2 的耗尽才会降低非刺激活性。 PLD2 减少的细胞在核周室中积累了更大比例的转铁蛋白受体，该受体对 Rab11（内体循环标记物）呈阳性。 EFA6 是 Arf6 的交换因子，已被提议刺激转铁蛋白受体的循环利用。因此，EFA6 过度表达的后果之一是内部受体库的减少。我们在对照 HeLa 细胞中证实了这一观察结果；然而，EFA6 的过度表达未能减少先前耗尽 PLD2 的细胞中积累的内部转铁蛋白受体池。这些观察结果表明，PLD2 是 Arf6 介导的组成型回收途径所必需的，或者在缺乏 PLD2 转铁蛋白受体的情况下，PLD2 转铁蛋白受体会在对 EFA6 过度表达不敏感的回收内体中积累。
RNA interference-mediated depletion of phospholipase D2 (PLD2), but not PLD1, inhibited recycling of transferrin receptors in HeLa cells, whereas the internalization rate was unaffected by depletion of either PLD. Although reduction of both PLD isoforms inhibits PLD activity stimulated by phorbol 12-myristic 13-acetate, only depletion of PLD2 decreased nonstimulated activity. Cells with reduced PLD2 accumulated a greater fraction of transferrin receptors in a perinuclear compartment that was positive for Rab11, a marker of recycling endosomes. EFA6, an exchange factor for Arf6, has been proposed to stimulate the recycling of transferrin receptors. Thus, one consequence of EFA6 overexpression would be a reduction of the internal pool of receptors. We confirmed this observation in control HeLa cells; however, overexpression of EFA6 failed to decrease the internal pool of transferrin receptors that accumulate in cells previously depleted of PLD2. These observations suggest that either PLD2 is required for a constitutive Arf6-mediated recycling pathway or in the absence of PLD2 transferrin receptors accumulate in recycling endosomes that are not responsive to overexpression of EFA6.