Regulation of Lipid-Droplet Transport by the Perilipin Homolog LSD2

Welte, Michael A.; Cermelli, Silvia; Griner, John; Viera, Arturo; Guo, Yi; Kim, Dae Hwan; Gindhart, Joseph G.; Gross, Steven P.

doi:10.1016/j.cub.2005.06.062

Cited by 149 publications

(202 citation statements)

References 39 publications

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“…Equal amounts (0.2 g, wet weight) of mycelia were incubated (6 h) in 10 ml of water or water supplemented with 0.1% bean root exudate (25) or 1% cuticle. Mycelia were also incubated in minimal medium (MM, glucose 10 g/liter, NaNO 3 6 g/liter, KCl 0.52 g/liter, MgSO 4 ⅐7H 2 O 0.52 g/liter, KH 2 PO 4 0.25 g/liter) or in hemolymph of Manduca sexta.…”

Section: Methodsmentioning

confidence: 99%

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The Metarhizium anisopliae Perilipin Homolog MPL1 Regulates Lipid Metabolism, Appressorial Turgor Pressure, and Virulence

Wang

Leger

2007

Journal of Biological Chemistry

185

163

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Cells store lipids in droplets. Studies addressing how mammals control lipid-based energy homeostasis have implicated proteins of the PAT domain family, such as perilipin that surrounds the lipid droplets. Perilipin knock-out mice are lean and resistant to obesity. Factors that mediate lipid storage in fungi are still unknown. Here we describe a gene (Mpl1) in the economically important insect fungal pathogen Metarhizium anisopliae that has structural similarities to mammalian perilipins. Consistent with a role in lipid storage, Mpl1 is predominantly expressed when M. anisopliae is engaged in accumulating lipids and ectopically expressed green fluorescent protein-tagged MPL1 (Metarhizium perilipin-like protein) localized to lipid droplets. Mutant M. anisopliae lacking MPL1 have thinner hyphae, fewer lipid droplets, particularly in appressoria (specialized infection structures at the end of germ tubes), and a decrease in total lipids. Mpl1 therefore acts in a perilipin-like manner suggesting an evolutionary conserved function in lipid metabolism. However, reflecting general differences between animal and fungal lineages, these proteins have also been selected to cope with different tasks. Thus, turgor generation by ⌬Mpl1 appressoria is dramatically reduced indicating that lipid droplets are required for solute accumulation. This was linked with the reduced ability to breach insect cuticle so that Mpl1 is a pathogenicity determinant. Blast searches of fungal genomes revealed that perilipin homologs are found only in pezizomycotinal ascomycetes and occur as single copy genes. Expression of Mpl1 in yeast cells, a fungus that lacks a perilipin-like gene, blocked their ability to mobilize lipids during starvation conditions. Eukaryotic cells contain droplets of triglycerides encased in phospholipid membranes. These lipid droplets (LDs) 3 were once considered to be just inert storage vessels for energy-rich fat, but recent studies have shown they have additional roles in maintaining membranes and moving components around cells. The lipid droplets have also been implicated in lipid diseases, inflammation, diabetes, cardiovascular disease, and liver disease (1). Consistent with fat droplets being metabolically active, the membranes encasing them have proteins with wide ranging biochemical activities. The best studied are mammalian proteins of the perilipin family (also called the PAT family) such as perilipin, adipocyte differentiation-related protein, and TIP47. These proteins have a characteristic series of hydrophobic sequences (the PAT domain) that facilitate their localization to the surface of lipid droplets. By coating droplets, perilipin forms a barrier that restricts the access of cytosolic lipases. During food deprivation, perilipin is phosphorylated by protein kinase A; the barrier function of perilipin is attenuated, and lipolysis increases (2). In comparison with normal mice, perilipin-deficient mice have less fat, more muscle, a higher metabolic rate, and are resistant to diet-induced and genetic obesity (3...

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Section: Methodsmentioning

confidence: 99%

“…3D) indicate that Mpl1 is not crucially involved in mediating the positioning of droplets in Metarhizium. This contrasts with Drosophila where perilipin regulates transportation of LDs (25). The pattern of LD distribution was also studied during formation of appressoria on locust hind wings.…”

Section: Loss Of Function Mutants Confirm That Mpl1 Plays Anmentioning

confidence: 99%

The Metarhizium anisopliae Perilipin Homolog MPL1 Regulates Lipid Metabolism, Appressorial Turgor Pressure, and Virulence

Wang

Leger

2007

Journal of Biological Chemistry

185

163

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“…Dynein (Gross et al 2000;Bostrom et al 2005) and kinesin-1 (Shubeita et al 2008) (minusend and plus-end motors, respectively) were found to associate with LDs. In Drosophila melanogaster, a PAT protein homolog, LSD2, regulates bidirectional LD movement by coordinating opposite-polarity motor proteins (Welte et al 2005). Overexpression and deficiency of LSD2 leads to obese and lean flies, respectively, indicating that LSD2 is required for normal lipid storage (Gronke et al 2003).…”

Section: Lipid Droplet Motilitymentioning

confidence: 99%

Not Just Fat: The Structure and Function of the Lipid Droplet

Fujimoto

Parton²

2011

Cold Spring Harbor Perspectives in Biology

398

336

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Lipid droplets (LDs) are independent organelles that are composed of a lipid ester core and a surface phospholipid monolayer. Recent studies have revealed many new proteins, functions, and phenomena associated with LDs. In addition, a number of diseases related to LDs are beginning to be understood at the molecular level. It is now clear that LDs are not an inert store of excess lipids but are dynamically engaged in various cellular functions, some of which are not directly related to lipid metabolism. Compared to conventional membrane organelles, there are still many uncertainties concerning the molecular architecture of LDs and how each function is placed in a structural context. Recent findings and remaining questions are discussed.

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“…On one side, inv is closely related in genome position, sequence and pattern of expression to engrailed (a segment polarity gene; Coleman et al, 1987). On the other side, Lsd-2 is related to the transportation of lipid particles along the microtubules and its regulation (Welte et al, 2005) as well as to lipid (Gronke et al, 2003) and triacylglycerol sequestering (Teixeira et al, 2003). In general, studies of the effect of Lsd-2 lack-of-function and gain-of-function mutations have shown that this gene is essential for an adjustment of the organismal lipid storage level.…”

Section: Body Size In Drosophilamentioning

confidence: 99%

Body size in Drosophila: genetic architecture, allometries and sexual dimorphism

2008

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Even though substantial progress has been made to elucidate the physiological and environmental factors underpinning differences in body size, little is known about its genetic architecture. Furthermore, all animal species bear a specific relationship between the size of each organ and overall body size, so different body size traits should be investigated as well as their sexual dimorphism that may have an important impact on the evolution of body size. We have surveyed 191 co-isogenic lines of Drosophila melanogaster, each one of them homozygous for a single P-element insertion, and assessed the effects of mutations on different body size traits compared to the P-element-free co-isogenic control. Nearly 60% of the lines showed significant differences with respect to the control for these traits in one or both sexes and almost 35% showed trait-and sex-specific effects. Candidate gene mutations frequently increased body size in males and decreased it in females. Among the 92 genes identified, most are involved in development and/or metabolic processes and their molecular functions principally include protein-binding and nucleic acid-binding activities. Although several genes showed pleiotropic effects in relation to body size, few of them were involved in the expression of all traits in one or both sexes. These genes seem to be important for different aspects related to the general functioning of the organism. In general, our results indicate that the genetic architecture of body size traits involves a large fraction of the genome and is largely sex and trait specific.

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Regulation of Lipid-Droplet Transport by the Perilipin Homolog LSD2

Abstract: LSD2 appears to represent a new class of regulators, a protein that transduces regulatory signals to a separable core motor machinery. In addition, the demonstration that LSD2 regulates both transport and lipid metabolism suggests a link between lipid-droplet motion and lipid homeostasis.

Cited by 149 publications

References 39 publications

The Metarhizium anisopliae Perilipin Homolog MPL1 Regulates Lipid Metabolism, Appressorial Turgor Pressure, and Virulence

The Metarhizium anisopliae Perilipin Homolog MPL1 Regulates Lipid Metabolism, Appressorial Turgor Pressure, and Virulence

Not Just Fat: The Structure and Function of the Lipid Droplet

Body size in Drosophila: genetic architecture, allometries and sexual dimorphism

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