Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route
Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route
复制标题
DOI：
10.1242/jcs.136598
复制
发表时间：
2014-03-01
影响因子：
4
通讯作者：
Polishchuk, Roman S.
中科院分区：
文献类型：
--
作者：
Capestrano, Mariagrazia;Mariggio, Stefania;Polishchuk, Roman S.
以往的研究表明，在生物合成和内吞途径中，膜管介导的转运事件需要磷脂酶A（2）（PLA（2））活性。在这里，我们表明，胞质磷脂酶A（2）β（cPLA（2）β，也称为PLA 2G 4 E）通过带正电荷的氨基酸的C-末端延伸靶向网格蛋白非依赖性内吞途径的膜室，这使得酶与富含网格蛋白非依赖性内体的磷酸肌醇脂质[特别是PI（4，5）P-2]相互作用。cPLA（2）β的消融抑制了管状元件的形成，所述管状元件将内化的网格蛋白非依赖性货物（例如MHC-I、CD 147和CD 55）运送回细胞表面，因此引起它们的细胞内滞留。cPLA（2）β通过小管形成支持再循环的能力依赖于酶的催化活性，因为失活的cPLA（2）β（S420 A）突变体不能恢复小管生长或从网格蛋白非依赖性内体转运。综上所述，我们的研究结果表明，cPLA（2）β是一个新的重要的调节剂的运输过程中的网格蛋白独立的内吞和再循环途径。cPLA（2）酶对该途径的亲和力支持了一个新的假设，即不同的PLA（2）酶在分泌和/或内吞系统的特定运输步骤中使用选择性靶向机制来局部调节小管形成。
Previous studies have demonstrated that membrane tubule-mediated transport events in biosynthetic and endocytic routes require phospholipase A(2) (PLA(2)) activity. Here, we show that cytosolic phospholipase A(2)epsilon (cPLA(2)epsilon, also known as PLA2G4E) is targeted to the membrane compartments of the clathrin-independent endocytic route through a C-terminal stretch of positively charged amino acids, which allows the enzyme to interact with phosphoinositide lipids [especially PI(4,5)P-2] that are enriched in clathrin-independent endosomes. Ablation of cPLA(2)epsilon suppressed the formation of tubular elements that carry internalized clathrin-independent cargoes, such as MHC-I, CD147 and CD55, back to the cell surface and, therefore, caused their intracellular retention. The ability of cPLA(2)epsilon to support recycling through tubule formation relies on the catalytic activity of the enzyme, because the inactive cPLA(2)epsilon(S420A) mutant was not able to recover either tubule growth or transport from clathrin-independent endosomes. Taken together, our findings indicate that cPLA(2)epsilon is a new important regulator of trafficking processes within the clathrin-independent endocytic and recycling route. The affinity of cPLA(2)epsilon for this pathway supports a new hypothesis that different PLA(2) enzymes use selective targeting mechanisms to regulate tubule formation locally during specific trafficking steps in the secretory and/or endocytic systems.