Control of Fat Storage by a Drosophila PAT Domain Protein

Grönke, Sebastian; Beller, Mathias; Fellert, Sonja; Ramakrishnan, Hariharasubramanian; Jäckle, Herbert; Kühnlein, Ronald P.

doi:10.1016/s0960-9822(03)00175-1

Cited by 260 publications

(304 citation statements)

References 13 publications

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“…An analysis of the amino acid sequence of Drosophila Lsdp1 and Lsd2 shows that these two proteins have 31.9% identity in a region of 119 amino acids localized toward the N terminus (residues 11-130 for Lsdp1 and residues 35-154 for Lsd2, respectively). This is the region in which the PAT domain localizes (36,37). A much lower similarity is found beyond this region.…”

Section: Discussionmentioning

confidence: 93%

“…melanogaster Lsdp1 has been previously recognized as a protein that shares similarity with the mammalian proteins of the PAT family, which is formed by a group of proteins such as Perilipins (Peri A), ADRP (adipose differentiation-related protein), and TIP47 (tail-interacting 47-kDa protein), that are associated with the lipid droplets (36). Only two insect proteins appear to belong to the PAT family, Lsdp1 and Lsd2 (36,37).…”

Section: Discussionmentioning

confidence: 99%

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Activation of the Lipid Droplet Controls the Rate of Lipolysis of Triglycerides in the Insect Fat Body

Patel

Soulages

Hariharasundaram

et al. 2005

Journal of Biological Chemistry

102

127

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The hydrolysis of triglyceride (TG) stored in the lipid droplets of the insect fat body is under hormonal regulation by the adipokinetic hormone (AKH), which triggers a rapid activation cAMP-dependent kinase cascade (protein kinase A (PKA)). The role of phosphorylation on two components of the lipolytic process, the TG-lipase and the lipid droplet, was investigated in fat body adipocytes. The activity of purified TG-lipase determined using in vivo TG-radiolabeled lipid droplets was unaffected by the phosphorylation of the lipase. However, the activity of purified lipase was 2.4-fold higher against lipid droplets isolated from hormone-stimulated fat bodies than against lipid droplets isolated from unstimulated tissue. In vivo stimulation of lipolysis promotes a rapid phosphorylation of a lipid droplet protein with an apparent mass of 42-44 kDa. This protein was identified as "Lipid Storage Droplet Protein 1" (Lsdp1). In vivo phosphorylation of this protein reached a peak ϳ10 min after the injection of AKH. Supporting a role of Lsdp1 in lipolysis, maximum TG-lipase activity was also observed with lipid droplets isolated 10 min after hormonal stimulation. The activation of lipolysis was reconstituted in vitro using purified insect PKA and TG-lipase and lipid droplets. In vitro phosphorylation of lipid droplets catalyzed by PKA enhanced the phosphorylation of Lsdp1 and the lipolytic rate of the lipase, demonstrating a prominent role PKA and protein phosphorylation on the activation of the lipid droplets. AKH-induced changes in the properties of the substrate do not promote a tight association of the lipase with the lipid droplets. It is concluded that the lipolysis in fat body adipocytes is controlled by the activation of the lipid droplet. This activation is achieved by PKA-mediated phosphorylation of the lipid droplet. Lsdp1 is the main target of PKA, suggesting that this protein is a major player in the activation of lipolysis in insects.Insects rely on lipid reserves to survive during physiological non-feeding periods or to meet the energy requirements of developing eggs, flight, and starvation. The fat body is the principal site for storage of both glycogen and lipids. The fat body synthesizes most of the proteins found in the hemolymph while also serving as the main storage site of triglycerides (TG), 1 which constitute Ͼ90% fat body lipids. Therefore, functionally, the fat body accomplishes roles that in vertebrates are carried out by both liver and adipose tissue (1).The tobacco hornworm, Manduca sexta, feeds constantly, and the content of fat body TG increases continuously until the end of the larval development. During the larval period (ϳ20 days), the content of TG in the fat body increases from a few micrograms to ϳ80 mg (2). During subsequent development, the lipid reserves are used to sustain the life of the adult insect, which feeds occasionally (2-5). Due to these metabolic features, M. sexta represents an excellent model for studying the basic mechanisms involved in either the synthesis/deposition o...

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Activation of the Lipid Droplet Controls the Rate of Lipolysis of Triglycerides in the Insect Fat Body

Patel

Soulages

Hariharasundaram

et al. 2005

Journal of Biological Chemistry

102

127

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“…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

402

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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Control of Fat Storage by a Drosophila PAT Domain Protein

Cited by 260 publications

References 13 publications

Activation of the Lipid Droplet Controls the Rate of Lipolysis of Triglycerides in the Insect Fat Body

Activation of the Lipid Droplet Controls the Rate of Lipolysis of Triglycerides in the Insect Fat Body

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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