cPLA2α and EHD1 interact and regulate the vesiculation of cholesterol-rich, GPI-anchored, protein-containing endosomes
cPLA2α and EHD1 interact and regulate the vesiculation of cholesterol-rich, GPI-anchored, protein-containing endosomes
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DOI：
10.1091/mbc.e11-10-0881
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发表时间：
2012-05-15
影响因子：
3.3
通讯作者：
Naslavsky, Naava
中科院分区：
文献类型：
--
作者：
Cai, Bishuang;Caplan, Steve;Naslavsky, Naava
脂质改性剂磷脂酶A2催化磷脂水解为倒锥形溶血磷脂，其有助于膜弯曲和/或微管化。关于胞质磷脂酶A2（cPLA 2）的功能及其在高尔基体和早期内体的膜调节中的作用，存在明确的发现。然而，没有研究涉及cPLA 2在调节含有糖基磷脂酰肌醇锚定蛋白（GPI-AP）的富含胆固醇的膜中的作用。我们的研究支持cPLA 2 α在含有GPI-AP的膜的囊泡形成中的作用，使用内源性CD 59作为GPI-AP的模型。在cPLA 2 α耗竭时，含CD 59的内体变得微管化。此外，溶血磷脂酰基转移酶抑制剂诱导的溶血磷脂的积累广泛囊泡化含CD 59的内体。然而，cPLA 2 α的过表达并没有增加内体囊泡形成，这意味着需要额外的因子。事实上，“pinchase”EHD 1，一个C-末端Eps 15同源结构域（EHD）ATP酶的耗竭，也诱导了含CD 59的内体的肥大。此外，EHD 1和cPLA 2 α在原位表现出相似性（
The lipid modifier phospholipase A2 catalyzes the hydrolysis of phospholipids to inverted-cone-shaped lysophospholipids that contribute to membrane curvature and/or tubulation. Conflicting findings exist regarding the function of cytosolic phospholipase A2 (cPLA2) and its role in membrane regulation at the Golgi and early endosomes. However, no studies addressed the role of cPLA2 in the regulation of cholesterol-rich membranes that contain glycosylphosphatidylinositol-anchored proteins (GPI-APs). Our studies support a role for cPLA2 alpha in the vesiculation of GPI-AP-containing membranes, using endogenous CD59 as a model for GPI-APs. On cPLA2 alpha depletion, CD59-containing endosomes became hypertubular. Moreover, accumulation of lysophospholipids induced by a lysophospholipid acyltransferase inhibitor extensively vesiculated CD59-containing endosomes. However, overexpression of cPLA2 alpha did not increase the endosomal vesiculation, implying a requirement for additional factors. Indeed, depletion of the "pinchase" EHD1, a C-terminal Eps15 homology domain (EHD) ATPase, also induced hypertubulation of CD59-containing endosomes. Furthermore, EHD1 and cPLA2 alpha demonstrated in situ proximity (