Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis.
Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis.
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DOI：
10.1091/mbc.e13-01-0026
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发表时间：
2013-06
影响因子：
3.3
通讯作者：
Caplan S
中科院分区：
文献类型：
--
作者：
Giridharan SS;Cai B;Vitale N;Naslavsky N;Caplan S
MICAL-L1和bar结构域蛋白syndapin2结合磷脂酸（PA），磷脂酸是循环内体（REs）的一种新型脂质成分。这些蛋白之间的相互作用稳定了它们与膜的结合，并通过syndapin2使小管成核。强调了PA在循环利用中的新作用，提出了管状RE形成的机制。内吞运输需要膜小管的产生及其随后的裂变来运输囊泡，以便对货物分子进行分类。内吞循环室是一组由Eps15同源结构域蛋白EHD1修饰的管状和囊状膜，负责受体和脂质循环到质膜。有人提出EHD二聚体结合和弯曲膜，从而产生循环核内体（RE）小管。然而，最近的研究表明，与CasL-Like1 （MICAL-L1）相互作用的分子（另一种最近发现的RE小管标记物）将EHD1招募到先前存在的小管中。支持管状循环内体产生的机制和事件尚不清楚。在此，我们提出了RE小管的生物发生机制。我们证明MICAL-L1和bar结构域蛋白syndapin2与磷脂酸结合，我们认为磷脂酸是RE的一种新的脂质成分。我们的研究表明，这两种蛋白之间的直接相互作用稳定了它们与膜的联系，允许syndapin2形成小管的成核。事实上，脂质体中磷脂酸的存在增强了syndapin2体外管化膜的能力。总的来说，我们的研究结果突出了磷脂酸在内吞循环中的新作用，并为管状REs的产生机制提供了新的见解。
MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid (PA), a novel lipid component of recycling endosomes (REs). Interactions between these proteins stabilize their association with membranes and allow nucleation of tubules by syndapin2. A new role is highlighted for PA in recycling, suggesting a mechanism for tubular RE formation. Endocytic transport necessitates the generation of membrane tubules and their subsequent fission to transport vesicles for sorting of cargo molecules. The endocytic recycling compartment, an array of tubular and vesicular membranes decorated by the Eps15 homology domain protein, EHD1, is responsible for receptor and lipid recycling to the plasma membrane. It has been proposed that EHD dimers bind and bend membranes, thus generating recycling endosome (RE) tubules. However, recent studies show that molecules interacting with CasL-Like1 (MICAL-L1), a second, recently identified RE tubule marker, recruits EHD1 to preexisting tubules. The mechanisms and events supporting the generation of tubular recycling endosomes were unclear. Here, we propose a mechanism for the biogenesis of RE tubules. We demonstrate that MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid, which we identify as a novel lipid component of RE. Our studies demonstrate that direct interactions between these two proteins stabilize their association with membranes, allowing for nucleation of tubules by syndapin2. Indeed, the presence of phosphatidic acid in liposomes enhances the ability of syndapin2 to tubulate membranes in vitro. Overall our results highlight a new role for phosphatidic acid in endocytic recycling and provide new insights into the mechanisms by which tubular REs are generated.