Molecular and Cellular Biochemistry

, Volume 326, Issue 1–2, pp 105–119 | Cite as

Circulatory lipid transport: lipoprotein assembly and function from an evolutionary perspective

  • Dick J. Van der Horst
  • Sigrid D. Roosendaal
  • Kees W. Rodenburg


Circulatory transport of neutral lipids (fat) in animals relies on members of the large lipid transfer protein (LLTP) superfamily, including mammalian apolipoprotein B (apoB) and insect apolipophorin II/I (apoLp-II/I). Latter proteins, which constitute the structural basis for the assembly of various lipoproteins, acquire lipids through microsomal triglyceride transfer protein (MTP)—another LLTP family member—and bind them by means of amphipathic structures. Comparative research reveals that LLTPs have evolved from the earliest animals and additionally highlights the structural and functional adaptations in these lipid carriers. For instance, in contrast to mammalian apoB, the insect apoB homologue, apoLp-II/I, is post-translationally cleaved by a furin, resulting in their appearance of two non-exchangeable apolipoproteins in the insect low-density lipoprotein (LDL) homologue, high-density lipophorin (HDLp). An important difference between mammalian and insect lipoproteins relates to the mechanism of lipid delivery. Whereas in mammals, endocytic uptake of lipoprotein particles, mediated via members of the LDL receptor (LDLR) family, results in their degradation in lysosomes, the insect HDLp was shown to act as a reusable lipid shuttle which is capable of reloading lipid. Although the recent identification of a lipophorin receptor (LpR), a homologue of LDLR, reveals that endocytic uptake of HDLp may constitute an additional mechanism of lipid delivery, the endocytosed lipoprotein appears to be recycled in a transferrin-like manner. Binding studies indicate that the HDLp–LpR complex, in contrast to the LDL–LDLR complex, is resistant to dissociation at endosomal pH as well as by treatment with EDTA mimicking the drop in Ca2+ concentration in the endosome. This remarkable stability of the ligand–receptor complex may provide a crucial key to the recycling mechanism. Based on the binding and dissociation capacities of mutant and hybrid receptors, the specific binding interaction of the ligand-binding domain of the receptor with HDLp was characterized. These structural similarities and functional adaptations of the lipid transport systems operative in mammals and insects are discussed from an evolutionary perspective.


Lipophorin Apolipophorin III Apolipoprotein LDL receptor Lipophorin receptor Diacylglycerol LLT domain MTP Lipoprotein recycling 


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Dick J. Van der Horst
    • 1
  • Sigrid D. Roosendaal
    • 1
  • Kees W. Rodenburg
    • 1
  1. 1.Division of Endocrinology and Metabolism, Department of Biology and Institute of BiomembranesUtrecht UniversityUtrechtThe Netherlands

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