Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes
Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes
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DOI：
10.1073/pnas.1109101108
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发表时间：
2011-09-20
影响因子：
11.1
通讯作者：
Arai, Hiroyuki
中科院分区：
文献类型：
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作者：
Uchida, Yasunori;Hasegawa, Junya;Arai, Hiroyuki
磷脂酰丝氨酸（PS）是生物膜的一种相对次要的成分。尽管其丰度低，但质膜（PM）中的PS在各种现象中起着关键作用，如凝血级联反应、清除凋亡细胞和募集信号分子。PS也定位于内吞细胞器中，但这与其细胞功能的关系仍不清楚。在这里，我们报告说，PS是必不可少的逆行膜交通在回收内体（RE）。PS是最集中的RE细胞内的细胞器，和evectin-2（evt-2），以前未知的功能的蛋白质，有针对性的RE的结合，其pleckstrin同源（PH）域PS。X射线分析支持PS与PH结构域结合的特异性。耗尽evt-2或掩蔽细胞内PS抑制膜交通从RE到高尔基体。这些发现揭示了控制RE到高尔基体转运的分子基础，并确定了一个独特的PH结构域，该结构域特异性识别PS而不是polyphosphoinositides。
Phosphatidylserine (PS) is a relatively minor constituent of biological membranes. Despite its low abundance, PS in the plasma membrane (PM) plays key roles in various phenomena such as the coagulation cascade, clearance of apoptotic cells, and recruitment of signaling molecules. PS also localizes in endocytic organelles, but how this relates to its cellular functions remains unknown. Here we report that PS is essential for retrograde membrane traffic at recycling endosomes (REs). PS was most concentrated in REs among intracellular organelles, and evectin-2 (evt-2), a protein of previously unknown function, was targeted to REs by the binding of its pleckstrin homology (PH) domain to PS. X-ray analysis supported the specificity of the binding of PS to the PH domain. Depletion of evt-2 or masking of intracellular PS suppressed membrane traffic from REs to the Golgi. These findings uncover the molecular basis that controls the RE-to-Golgi transport and identify a unique PH domain that specifically recognizes PS but not polyphosphoinositides.