具有生物活性的信號作用脂質(zhì)“神經(jīng)酰胺-1-磷酸鹽”(C1P) 調(diào)控從生長和生存到“促炎反應(yīng)”在內(nèi)的各種不同過程,。在這項研究中,，Dinshaw Patel及同事研究了C1P是怎樣被輸送到細(xì)胞中的特定點的,。他們識別出被稱為“神經(jīng)酰胺-1-磷酸鹽轉(zhuǎn)移蛋白”(CPTP)的一種新穎的脂質(zhì)轉(zhuǎn)移蛋白,，同時結(jié)構(gòu)和功能研究也顯示了C1P被從其在“高爾基”復(fù)合體中的合成點輸送到胞質(zhì)膜上的機制。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi: 10.1038/nature12332
Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids
Dhirendra K. Simanshu, Ravi Kanth Kamlekar, Dayanjan S. Wijesinghe, Xianqiong Zou, Xiuhong Zhai, Shrawan K. Mishra, Julian G. Molotkovsky Lucy Malinina, Edward H. Hinchcliffe, Charles E. Chalfant, Rhoderick E. Brown, Dinshaw J. Patel
Phosphorylated sphingolipids ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) have emerged as key regulators of cell growth, survival, migration and inflammation. C1P produced by ceramide kinase is an activator of group IVA cytosolic phospholipase A2α (cPLA2α), the rate-limiting releaser of arachidonic acid used for pro-inflammatory eicosanoid production, which contributes to disease pathogenesis in asthma or airway hyper-responsiveness, cancer, atherosclerosis and thrombosis. To modulate eicosanoid action and avoid the damaging effects of chronic inflammation, cells require efficient targeting, trafficking and presentation of C1P to specific cellular sites. Vesicular trafficking is likely but non-vesicular mechanisms for C1P sensing, transfer and presentation remain unexplored. Moreover, the molecular basis for selective recognition and binding among signalling lipids with phosphate headgroups, namely C1P, phosphatidic acid or their lyso-derivatives, remains unclear. Here, a ubiquitously expressed lipid transfer protein, human GLTPD1, named here CPTP, is shown to specifically transfer C1P between membranes. Crystal structures establish C1P binding through a novel surface-localized, phosphate headgroup recognition centre connected to an interior hydrophobic pocket that adaptively expands to ensheath differing-length lipid chains using a cleft-like gating mechanism. The two-layer, α-helically-dominated ‘sandwich’ topology identifies CPTP as the prototype for a new glycolipid transfer protein fold13 subfamily. CPTP resides in the cell cytosol but associates with the trans-Golgi network, nucleus and plasma membrane. RNA interference-induced CPTP depletion elevates C1P steady-state levels and alters Golgi cisternae stack morphology. The resulting C1P decrease in plasma membranes and increase in the Golgi complex stimulates cPLA2α release of arachidonic acid, triggering pro-inflammatory eicosanoid generation.
