Lipoprotein-mediated lipid transport in insects: Analogy to the mammalian lipid carrier system and novel concepts for the functioning of LDL receptor family members

Rodenburg, Kees W.; Horst, Dick J. Van der

doi:10.1016/j.bbalip.2005.07.002

Cited by 51 publications

(79 citation statements)

References 139 publications

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“…Both the yolk Vtgs and apolipophorins of insects are produced by the fat body and circulated through the body via the hemolymph (Rodenburg and Van der Horst, 2005;Ziegler and Van Antwerpen, 2006). The same is probably true for Cv-d. We detected cv-d message by RT-PCR from dissected larval fat body (Fig.…”

Section: Cv-d Can Be Transported Into the Wing By Hemolymphmentioning

confidence: 77%

Crossveinless d is a vitellogenin-like lipoprotein that binds BMPs and HSPGs, and is required for normal BMP signaling in the Drosophila wing

et al. 2012

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SUMMARYThe sensitivity of the posterior crossvein in the pupal wing of Drosophila to reductions in the levels and range of BMP signaling has been used to isolate and characterize novel regulators of this pathway. We show here that crossveinless d (cv-d) mutations, which disrupt BMP signaling during the development of the posterior crossvein, mutate a lipoprotein that is similar to the vitellogenins that comprise the major constituents of yolk in animal embryos. Cv-d is made in the liver-like fat body and other tissues, and can diffuse into the pupal wing via the hemolymph. Cv-d binds to the BMPs Dpp and Gbb through its Vg domain, and to heparan sulfate proteoglycans, which are well-known for their role in BMP movement and accumulation in the wing. Cv-d acts over a long range in vivo, and does not have BMP co-receptor-like activity in vitro. We suggest that, instead, it affects the range of BMP movement in the pupal wing, probably as part of a lipid-BMP-lipoprotein complex, similar to the role proposed for the apolipophorin lipid transport proteins in Hedgehog and Wnt movement.

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Section: Cv-d Can Be Transported Into the Wing By Hemolymphmentioning

confidence: 77%

Crossveinless d is a vitellogenin-like lipoprotein that binds BMPs and HSPGs, and is required for normal BMP signaling in the Drosophila wing

et al. 2012

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“…Significantly, no such accumulation occurred with loss of spectrin function, indicating that lipophorin continues to transport dietary lipid in the absence of cortical lipid droplets in the fat body. Alternative mechanisms may include (1) endocytosis of lipophorin (Rodenburg and Van Der Horst 2005), (2) a pathway that feeds directly into large lipid droplets, or (3) delivery of dietary lipids to an alternate site [e.g., oenocytes were previously shown to be a lipophorin destination during starvation (Gutierrez et al 2007)]. Further experiments will be needed to address this issue.…”

Section: Implications For Redundant Functionmentioning

confidence: 99%

Genetic Studies of Spectrin in the Larval Fat Body ofDrosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

et al. 2013

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Spectrin cytoskeleton defects produce a host of phenotypes affecting the plasma membrane, cell polarity, and secretory membrane traffic. However, many of the underlying molecular mechanisms remain unexplained by prevailing models. Here we used the larval fat body of Drosophila melanogaster as a genetic model system to further elucidate mechanisms of ab-spectrin function. The results provide unexpected new insights into spectrin function as well as mechanisms of dietary fat uptake and storage. We show that loss of a-or b-spectrin in the fat body eliminated a population of small cortical lipid droplets and altered plasma membrane architecture, but did not affect viability of the organism. We present a novel model in which ab-spectrin directly couples lipid uptake at the plasma membrane to lipid droplet growth in the cytoplasm. In contrast, strong overexpression of b-spectrin caused fat body atrophy and larval lethality. Overexpression of b-spectrin also perturbed transport of dietary fat from the midgut to the fat body. This hypermorphic phenotype appears to be the result of blocking secretion of the lipid carrier lipophorin from fat cells. However, this midgut phenotype was never seen with spectrin loss of function, suggesting that spectrin is not normally required for lipophorin secretion or function. The b-spectrin hypermorphic phenotype was ameliorated by co-overexpression of a-spectrin. Based on the overexpression results here, we propose that b-spectrin family members may be prone to hypermorphic effects (including effects on secretion) if their activity is not properly regulated. MEMBERS of the spectrin and ankyrin gene families are ubiquitous in animal cells and defects in these genes are responsible for a range of inherited human disorders, including spinocerebellar ataxia type 5 (SCA5) (Ikeda et al. 2006), anemia (Lux andPalek 1995), and Duchenne muscular dystrophy (Koenig et al. 1988). In most cases, the precise molecular mechanisms underlying the disease process are incompletely understood. Spectrin and ankyrin are most familiar as components of a subplasma membrane protein scaffold known as the spectrin cytoskeleton (Baines 2010). In one long-standing hypothesis the spectrin cytoskeleton is thought to capture and stabilize interacting membrane proteins as they arrive at the cell surface, creating domains of specialized composition and function (Dubreuil 2006).Recent genetic studies in a number of model systems suggest that spectrin and ankyrin have further roles in intracellular membrane traffic (Kizhatil et al. 2007(Kizhatil et al. , 2009Ayalon et al. 2008;Stabach et al. 2008;Clarkson et al. 2010;Lorenzo et al. 2010;Tjota et al. 2011).Given the conservation of spectrin and ankyrin genes between vertebrates and invertebrates, one would expect that their functions should also be conserved. Indeed, as is the case in vertebrates, loss-of-function mutations of a-and b-spectrin and ankyrin2 in Drosophila are lethal early in development (Lee et al. 1993;Dubreuil et al. 2000;Koch et al. 2008;Pielag...

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“…In non-polarized mammalian cells, this FxNPxY signal is entirely responsible for the rapid internalization of the LDL receptor (Chen et al, 1990;Davis et al, 1986). In most instances the function of this putative endocytic sorting signal has not been directly verified in insects, yet both the vitellogenin and lipophorin receptors internalize bound ligands into the developing oocyte and recycle back to the cell surface (Atella et al, 2006;Rodenburg and Van der Horst, 2005;Seo et al, 2003;Snigirevskaya et al, 1997;Sun et al, 2000). The significant conservation of the key specificity-determining residues and positioning relative to the membrane surface therefore suggests that, as in chordates, invertebrate PTB-domain clathrin-associated sorting proteins (CLASPs) might decode this sorting signal to ensure efficient receptor endocytosis in insect cells.…”

Section: Resultsmentioning

confidence: 99%

“…It is also known that A. aegypti ovarioles are patent from an early, previtellogenic stage (Anderson and Spielman, 1971;Raikhel and Lea, 1985), allowing ligands access to surface-positioned receptors. Although vitellogenin levels are low before a blood meal, lipophorin levels must be normal, because lipophorin is an energy carrier required for flight as well as basic cell metabolism (Rodenburg and Van der Horst, 2005). Nutritionally regulated trephin gene transcription may allow selective uncoupling of LDL receptor gene family members from clathrin-mediated endocytosis in previtellogenic ovaries, thus preventing precocious yolk granule accumulation that might be deleterious.…”

Section: Discussionmentioning

confidence: 99%

“…Rather, the major site of yolk protein synthesis is the fat body, an arthropod organ that is a functional hybrid of the vertebrate liver and adipocyte combined (Rodenburg and Van der Horst, 2005). In adult female mosquitoes, the fat body synthesizes both vitellogenin (a lipophosphoglycoprotein) and lipophorin [a lipid-rich lipoprotein particle resembling mammalian low density lipoprotein (LDL)], which are secreted directly into the hemolymph.…”

Section: Introductionmentioning

confidence: 99%

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Internalization of LDL-receptor superfamily yolk-protein receptors during mosquito oogenesis involves transcriptional regulation of PTB-domain adaptors

Mishra

Jha

Steinhauser

et al. 2008

Journal of Cell Science

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In the anautogenous disease vector mosquitoes Anopheles gambiae and Aedes aegypti, egg development is nutritionally controlled. A blood meal permits further maturation of developmentally repressed previtellogenic egg chambers. This entails massive storage of extraovarian yolk precursors by the oocyte, which occurs through a burst of clathrin-mediated endocytosis. Yolk precursors are concentrated at clathrin-coated structures on the oolemma by two endocytic receptors, the vitellogenin and lipophorin receptors. Both these mosquito receptors are members of the low-density-lipoprotein-receptor superfamily that contain FxNPxY-type internalization signals. In mammals, this tyrosine-based signal is not decoded by the endocytic AP-2 adaptor complex directly. Instead, two functionally redundant phosphotyrosine-binding domain adaptors, Disabled 2 and the autosomal recessive hypercholesterolemia protein (ARH) manage the internalization of the FxNPxY sorting signal. Here, we report that a mosquito ARH-like protein, which we designate trephin, possess similar functional properties to the orthologous vertebrate proteins despite engaging AP-2 in an atypical manner, and that mRNA expression in the egg chamber is strongly upregulated shortly following a blood meal. Temporally regulated trephin transcription and translation suggests a mechanism for controlling yolk uptake when vitellogenin and lipophorin receptors are expressed and clathrin coats operate in previtellogenic ovaries.

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Lipoprotein-mediated lipid transport in insects: Analogy to the mammalian lipid carrier system and novel concepts for the functioning of LDL receptor family members

Cited by 51 publications

References 139 publications

Crossveinless d is a vitellogenin-like lipoprotein that binds BMPs and HSPGs, and is required for normal BMP signaling in the Drosophila wing

Crossveinless d is a vitellogenin-like lipoprotein that binds BMPs and HSPGs, and is required for normal BMP signaling in the Drosophila wing

Genetic Studies of Spectrin in the Larval Fat Body ofDrosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

Internalization of LDL-receptor superfamily yolk-protein receptors during mosquito oogenesis involves transcriptional regulation of PTB-domain adaptors

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