Lipoprotein Particles Cross the Blood-Brain Barrier in Drosophila
Lipoprotein Particles Cross the Blood-Brain Barrier in Drosophila
复制标题
DOI：
10.1523/jneurosci.5943-09.2010
复制
发表时间：
2010-08-04
影响因子：
5.3
通讯作者：
Eaton, Suzanne
中科院分区：
文献类型：
--
作者：
Brankatschk, Marko;Eaton, Suzanne
血脑屏障（BBB）调节营养物质和信号分子从循环进入大脑的通道。脂蛋白是否能在体内穿过血脑屏障一直存在争议，也没有明确的证据表明循环脂蛋白在脑发育中的作用。我们在果蝇中解决这些问题，果蝇具有功能保守的血脑屏障和类似于脊椎动物的脂蛋白。我们表明，果蝇脂蛋白lipophorin存在两种亚型。两种亚型都穿过BBB，但在脑内不同的细胞亚群上积累。除了作为脂质载体外，载脂蛋白还携带固醇连接和GPI连接的蛋白质进入循环并将其转运穿过BBB。最后，载脂蛋白通过一种不依赖于膳食脂质递送的机制促进成神经细胞增殖。脂转运蛋白及其货物通过血脑屏障代表了一种新的机制，通过这种机制，外周合成的蛋白质可能进入大脑并影响其发育。此外，脂质连接可能是一种有效的方法来运输治疗分子通过血脑屏障。
The blood-brain barrier (BBB) regulates passage of nutrients and signaling molecules from the circulation into the brain. Whether lipoproteins cross the BBB in vivo has been controversial, and no clear requirement for circulating lipoproteins in brain development has been shown. We address these issues in Drosophila, which has an functionally conserved BBB, and lipoproteins that resemble those of vertebrates. We show that the Drosophila lipoprotein lipophorin exists in two isoforms. Both isoforms cross the BBB, but accumulate on distinct subsets of cells within the brain. In addition to acting as a lipid carrier, lipophorin carries both sterol-linked and GPI-linked proteins into the circulation and transports them across the BBB. Finally, lipophorin promotes neuroblast proliferation by a mechanism that does not depend on delivery of dietary lipids. Transport of lipophorin and its cargo across the BBB represents a novel mechanism by which peripherally synthesized proteins might enter the brain and influence its development. Furthermore, lipid-linkage may be an efficient method to transport therapeutic molecules across the BBB.