Lipoprotein Particles Cross the Blood–Brain Barrier in<i>Drosophila</i>

Brankatschk, Marko; Eaton, Suzanne

doi:10.1523/jneurosci.5943-09.2010

Cited by 97 publications

(88 citation statements)

References 30 publications

(37 reference statements)

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“…These findings raise the possibility that Hh may have systemic functions in addition to its role as a morphogen. In Drosophila, evidence that lipophorin crosses the blood-brain barrier and is necessary for neuroblast proliferation has been interpreted to indicate that lipoprotein particles may have roles that are independent of lipid delivery [123]. Thus, the question whether lipoprotein-association is relevant to contexts such as the Hh signaling gradient in the wing disk is important but not yet answered.…”

Section: Lipoprotein Particlesmentioning

confidence: 99%

Hedgehog and its circuitous journey from producing to target cells

Guerrero

Kornberg

2014

Seminars in Cell & Developmental Biology

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a b s t r a c tThe hedgehog (Hh) signaling protein has essential roles in the growth, development and regulation of many vertebrate and invertebrate organs. The processes that make Hh and prepare it for release from producing cells and that move it to target cells are both diverse and complex. This article reviews the essential features of these processes and highlights recent work that provides a novel framework to understand how these processes contribute to an integrated pathway.

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Section: Lipoprotein Particlesmentioning

confidence: 99%

Hedgehog and its circuitous journey from producing to target cells

Guerrero

Kornberg

2014

Seminars in Cell & Developmental Biology

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“…The lace mutant l(2)k05305 has been described previously (Adachi-Yamada et al, 1999). GAL4 lines used were: tubulinGAL4, elavGAL4 and adhGAL4 (Bloomington), npc1bGAL4 (Voght et al, 2007) and lipoGAL4 (Brankatschk and Eaton, 2010).…”

Section: Fliesmentioning

confidence: 99%

Survival strategies of a sterol auxotroph

et al. 2010

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SUMMARYThe high sterol concentration in eukaryotic cell membranes is thought to influence membrane properties such as permeability, fluidity and microdomain formation. Drosophila cannot synthesize sterols, but do require them for development. Does this simply reflect a requirement for sterols in steroid hormone biosynthesis, or is bulk membrane sterol also essential in Drosophila? If the latter is true, how do they survive fluctuations in sterol availability and maintain membrane homeostasis? Here, we show that Drosophila require both bulk membrane sterol and steroid hormones in order to complete adult development. When sterol availability is restricted, Drosophila larvae modulate their growth to maintain membrane sterol levels within tight limits. When dietary sterol drops below a minimal threshold, larvae arrest growth and development in a reversible manner. Strikingly, membrane sterol levels in arrested larvae are dramatically reduced (dropping sixfold on average) in most tissues except the nervous system. Thus, sterols are dispensable for maintaining the basic membrane biophysical properties required for cell viability; these functions can be performed by non-sterol lipids when sterols are unavailable. However, bulk membrane sterol is likely to have essential functions in specific tissues during development. In tissues in which sterol levels drop, the overall level of sphingolipids increases and the proportion of different sphingolipid variants is altered. These changes allow survival, but not growth, when membrane sterol levels are low. This relationship between sterols and sphingolipids could be an ancient and conserved principle of membrane homeostasis.

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“…13) Although lipoprotein particles can cross the BBB in vivo in Drosophila, which has a functional BBB like that in vertebrates, 14) lipoproteins in the mouse, rat and human do not cross the BBB. Consequently, since labeled cholesterol peripherally administrated was not found in the CNS of mammals, 15,16) cholesterol in the CNS is derived from de novo synthesis inside of the CNS.…”

Section: Lipid Homeostasis In the Cnsmentioning

confidence: 99%

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Hayashi

2011

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFunctions of the central nervous system (CNS) are performed mainly by neurons and glia-primarily astrocytes, microglia and oligodendrocytes. It has been thought for a long time that glia only passively support neurons, but we now know that glia actively attend to assist in neuronal functions like synaptogenesis and neurotransmission. 1) Although it was believed that ca. 90% of the cells in the brain are glia and the rest of cells are neurons, Azevedo et al. recently reported that the numbers of neurons and non-neuronal cells (glia) are close to equal in human adult brain.2) Brain is the most cholesterol-rich organ in the body, and cholesterol metabolism in the CNS is tightly regulated between neurons and glia. [3][4][5][6][7] Imbalances in the metabolism of lipids, especially cholesterol, are closely linked to the development of several neurodegenerative disorders such as Alzheimer's disease, 8,9) Niemann-Pick type C disease 10) and Smith-Lemli Opitz syndrome. 11,12) In this review the regulation of lipid metabolism and the roles of glial lipoproteins in the CNS will be discussed. LIPID HOMEOSTASIS IN THE CNSThe system of lipid metabolism and transport in the CNS is different from that in peripheral tissues because the CNS is segregated from the peripheral circulation by the blood-brain barrier (BBB).13) Although lipoprotein particles can cross the BBB in vivo in Drosophila, which has a functional BBB like that in vertebrates, 14) lipoproteins in the mouse, rat and human do not cross the BBB. Consequently, since labeled cholesterol peripherally administrated was not found in the CNS of mammals, 15,16) cholesterol in the CNS is derived from de novo synthesis inside of the CNS. Furthermore, in the plasma of subjects who had liver transplantation the genotype of apolipoprotein (apo) E was that of the donor, whereas the subjects retained the own apo E genotype in the cerebrospinal fluid (CSF).17) Moreover, lipoproteins in the CNS consist of only high density lipoprotein (HDL)-like particles in contrast to the circulation which contains very low density lipoproteins (VLDL), low density lipoproteins (LDL) and HDL. It is known that the HDL-like particles in the CNS are secreted from glia (glial lipoproteins), mainly astrocytes and microglia, under normal conditions, [18][19][20] however lipoproteins can be secreted from neurons in vitro 21,22) and in vivo 23) under some specific conditions. Unesterified cholesterol is the major sterol in the adult brain, and small amounts of desmosterol and cholesteryl ester are also present. The majority (70-80%) of cholesterol in the adult brain is in myelin formed by oligodendrocytes. 24)Thus, the activity of cholesterol synthesis in the CNS is the highest during the myelinogenesis. After myelination, cholesterol synthesis continues at very low level in the CNS, and occurs mainly in astrocytes. 5,13,24) Neurons do not efficiently synthesize cholesterol and rely on external source of cholesterol from astrocytes, 25) so that neurons take up cholesterol as lipoproteins via ...

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Lipoprotein Particles Cross the Blood–Brain Barrier inDrosophila

Cited by 97 publications

References 30 publications

Hedgehog and its circuitous journey from producing to target cells

Hedgehog and its circuitous journey from producing to target cells

Survival strategies of a sterol auxotroph

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

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