title: Lipoprotein assembly and function in an evolutionary perspective.
abstract: Circulatory fat transport 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). ApoB and apoLp-II/I, constituting the structural (non-exchangeable) basis for the assembly of various lipoproteins, acquire lipids through microsomal triglyceride-transfer protein, another LLTP family member, and bind them by means of amphipathic α-helical and β-sheet structural motifs. Comparative research reveals that LLTPs evolved from the earliest animals and highlights the structural adaptations in these lipid-binding proteins. Thus, in contrast to apoB, apoLp-II/I is cleaved post-translationally by a furin, resulting in the appearance of two non-exchangeable apolipoproteins in the single circulatory lipoprotein in insects, high-density lipophorin (HDLp). The remarkable structural similarities between mammalian and insect lipoproteins notwithstanding important functional differences relate to the mechanism of lipid delivery. Whereas in mammals, partial delipidation of apoB-containing lipoproteins eventually results in endocytic uptake of their remnants, mediated by members of the low-density lipoprotein receptor (LDLR) family, and degradation in lysosomes, insect HDLp functions as a reusable lipid shuttle capable of alternate unloading and reloading of lipid. Also, during muscular efforts (flight activity), an HDLp-based lipoprotein shuttle provides for the transport of lipid for energy generation. Although a lipophorin receptor - a homolog of LDLR - was identified that mediates endocytic uptake of HDLp during specific developmental periods, the endocytosed lipoprotein appears to be recycled in a transferrin-like manner. These data highlight that the functional adaptations in the lipoprotein lipid carriers in mammals and insects also emerge with regard to the functioning of their cognate receptors.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Van der Horst
authors.forename: Kees W
authors.initials: KW
authors.lastname: Rodenburg