LIPID AND LIPOPROTEIN METABOLISM IN INSECTS

点击翻译按钮获取中文摘要

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.