LIPID AND LIPOPROTEIN METABOLISM IN INSECTS

本研究的长期目标是确定基本机制 参与昆虫的脂质运输和储存;为了发现 这些机制是昆虫特有的， 生物控制昆虫;并确定这些机制 可作为了解脊椎动物脂质转运的模型。 而脊椎动物依靠一系列脂蛋白来影响脂质 运输，昆虫主要使用单一类型的脂蛋白，脂蛋白， 用于脂质运输。脂转运蛋白比脊椎动物更通用 脂蛋白在它运输的各种脂质方面， 在大多数情况下，它比脊椎动物脂蛋白更有效， 将脂质递送到组织而自身不被内化， 摧毁.载脂蛋白在其核心可以携带多种脂质，其中 甘油二酯（DG）是主要成分。载脂蛋白是由脂肪 作为含有载脂蛋白的新生脂蛋白体， 磷脂，但没有DG或其他转运脂质。DG收购自 中肠并运输到脂肪体中储存。运输 DG从中肠到脂肪体是由两种脂转运蛋白受体介导的： 特异性结合DG-贫载脂蛋白的中肠， 促进DG从中肠到载脂蛋白的移动，另一个在 脂肪体，其特异性结合富含DG的载脂蛋白， 促进DG从载脂蛋白向脂肪体的移动。具体目标1是 旨在纯化和鉴定这些受体。飞行期间所 从许多物种的成虫，脂肪体甘油三酯商店是 转化为DG，离开脂肪体并被载脂蛋白吸收 在血淋巴中，然后被运送到飞行肌肉，在那里， DG被转化为脂肪酸，脂肪酸被氧化以提供能量 飞行所需的。脂转运蛋白对DG的摄取依赖于 可溶性载脂蛋白，载脂蛋白-III（apoLpIII）， 游离于血淋巴中。 ApoLp-III与载脂蛋白结合， 增加了它携带DG的能力。最近，apoLp的X射线结构- 三是确定了。具体目标2旨在研究机制 由此apoLp-III结合脂蛋白表面。的另一个特点 载脂蛋白代谢是其将特定脂质递送至 特定组织鉴于载脂蛋白携带复杂的混合物， 脂质，如何选择性地将特定的脂质递送到特定的 组织发生？ 待检验的假设是组织特异性 脂质递送需要两个组成部分：1）特异性脂质结合 组织细胞内的蛋白质和2）非内化的 脂蛋白受体的细胞表面的组织。具体 目的3旨在通过研究类胡萝卜素转运来验证这一假设 在家蚕中，其中几个突变体在类胡萝卜素运输， 系统存在。

The long-term goals of this research are to determine the basic mechanisms involved in lipid transport and storage in insects; to discover which of these mechanisms are specific to insects and might be targets for biorational control of insects; and to ascertain which of these mechanisms can be used as models for understanding lipid transport in vertebrates. Whereas vertebrates rely on a battery of lipoproteins to effect lipid transport, insects use primarily a single type of lipoprotein, LIPOPHORIN, for lipid transport. Lipophorin is both more versatile than vertebrate lipoproteins in terms of the diverse lipids it transports and more efficient than vertebrate lipoproteins in that, for the most part, it delivers lipids to tissues without itself being internalized and destroyed. Lipophorin can carry a variety of lipids in its core, of which diacylglycerol (DG) is the major component. Lipophorin is made in the fat body as a nascent lipoprotein which contains apolipoproteins and phospholipid, but no DG or other transported lipids. DG is acquired from the midgut and transported to the fat body for storage. The transport of DG from midgut to fat body is mediated by two lipophorin receptors: one in the midgut which specifically binds DG-poor lipophorin and which facilitates movement of DG from midgut to lipophorin, and another in the fat body, which specifically binds DG-rich lipophorin and which facilitates movement of DG from lipophorin to fat body. Specific Aim 1 is designed to purify and characterize these receptors. During flight in adult insects from many species, fat body triacylglycerol stores are converted to DG, which leaves the fat body and is taken up by lipophorin in the hemolymph, and then is transported to the flight muscle, where the DG is converted to fatty acids which are oxidized to provide the energy required for flight. The uptake of DG by lipophorin is dependent on a soluble apolipoprotein, apolipophorin-III (apoLpIII), which is present free in the hemolymph. ApoLp-III binds to lipophorin and greatly increases it capacity to carry DG. Recently, the x-ray structure of apoLp- III has been determined. Specific Aim 2 is designed to study the mechanism whereby apoLp-III binds to lipoprotein surfaces. Another hallmark of lipophorin metabolism is its ability to deliver specific lipids to specific tissues. Given that lipophorin carries a complex mixture of lipids, how does selective delivery of a specific lipid to a specific tissue occur? The hypothesis to be tested is that the tissue specificity of lipid delivery requires two components: 1) a specific lipid-binding protein within the cells of the tissue and 2) a non-internalizing lipoprotein receptor on the surface of the cells of the tissue. Specific Aim 3 is designed to test this hypothesis by studying carotenoid transport in Bombyx mori, in which several mutants in the carotenoid transport system exist.