The evolutionary conserved protein CG9186 is associated with lipid droplets, required for their positioning and for fat storage.

Journal of Cell Science (Impact Factor: 5.43). 03/2013; 126(10). DOI: 10.1242/jcs.120493
Source: PubMed


Lipid droplets (LDs) represent specialized cell organelles for the storage of energy rich lipids. Although lipid storage is a conserved feature of all cells and organisms, only little is known about fundamental aspects of the cell biology of LDs, including their biogenesis, structural assembly and subcellular positioning, and the regulation of organismic energy homeostasis.We identified a novel LD-associated protein family, represented by the Drosophila protein CG9186 and its murine homolog MGI:1916082. In the absence of LDs, both proteins localize at the endoplasmic reticulum (ER). Upon lipid storage induction, they translocate to LDs using an evolutionary conserved targeting mechanism that acts via a 60 amino acids targeting motif in the center of the CG9186 protein. Overexpression of CG9186 and MGI:1916082 causes clustering of LDs in both tissue culture and salivary gland cells, whereas the RNAi knockdown results in a reduction of LDs. Organismal RNAi knock-down of CG9186 results in a reduction of the lipid storage levels of the fly. The results indicate that we identified the first members of a novel and evolutionary conserved family of lipid storage regulators, which are also required to properly position LDs within cells.

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    • "Several proteins that function in ERAD to extract proteins from the ER are colocalized to ER and droplets. These include derlin-1, UBXD2, UBXD8, p97/VCP, and AUP1 (Suzuki et al., 2012; Olzmann et al., 2013; Stevanovic and Thiele, 2013). Evidence for colocalization is their appearance in proteomes of isolated droplets, and live and fixed cell fluorescence with antibodies or tagged proteins. "
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    ABSTRACT: Our knowledge of inter-organellar communication has grown exponentially in recent years. This review focuses on the interactions that cytoplasmic lipid droplets have with other organelles. Twenty-five years ago droplets were considered simply particles of coalesced fat. Ten years ago there were hints from proteomics studies that droplets might interact with other structures to share lipids and proteins. Now it is clear that the droplets interact with many if not most cellular structures to maintain cellular homeostasis and to buffer against insults such as starvation. The evidence for this statement, as well as probes to understand the nature and results of droplet interactions, are presented.
    Frontiers in Cell and Developmental Biology 08/2015; 3:49. DOI:10.3389/fcell.2015.00049
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    • "Interestingly, in both cases mammalian cells show similar phenotypes upon mutation or inhibition of the respective orthologous proteins [45], [46], indicating conservation of the unknown underlying mechanisms. In a recent study in Drosophila melanogaster, overexpression of a GFP-tagged putative hydrolase also lead to formation of LD clusters [47]. "
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    ABSTRACT: Lipid droplets, the intracellular storage organelles for neutral lipids, exist in a wide range of sizes and of morphologically distinct organization, from loosely dispersed lipid droplets to tightly packed lipid droplet clusters. We show that the lipid droplet protein AUP1 induces cluster formation. A fraction of AUP1 is monoubiquitinated at various lysine residues. This process depends on its internal CUE domain, which is a known ubiquitin-binding domain. AUP1 with a deleted or point mutagenized CUE domain, as well as a lysine-free mutant, are not ubiquitinated and do not induce lipid droplet clustering. When such ubiquitination deficient mutants are fused to ubiquitin, clustering is restored. AUP1 mutants with defective droplet targeting fail to induce clustering. Also, another lipid droplet protein, NSDHL, with a fused ubiquitin does not induce clustering. The data indicate that monoubiquitinated AUP1 on the lipid droplet surface specifically induces clustering, and suggest a homophilic interaction with a second AUP1 molecule or a heterophilic interaction with another ubiquitin-binding protein.
    PLoS ONE 09/2013; 8(9):e72453. DOI:10.1371/journal.pone.0072453 · 3.23 Impact Factor
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    ABSTRACT: The transition from a liquid to a gas filled tubular network is the prerequisite for normal function of vertebrate lungs and invertebrate tracheal systems. However, the mechanisms underlying the process of gas filling remain obscure. Here we show that waterproof, encoding a fatty acyl-CoA reductase (FAR), is essential for the gas filling of the tracheal tubes during Drosophila embryogenesis, and does not affect branch network formation or key tracheal maturation processes. However, electron microscopic analysis reveals that in waterproof mutant embryos the formation of the outermost tracheal cuticle sublayer, the envelope, is disrupted and the hydrophobic tracheal coating is damaged. Genetic and gain-of-function experiments indicate a non-cell-autonomous waterproof function for the beginning of the tracheal gas filling process. Interestingly, Waterproof reduces very long chain fatty acids of 24 and 26 carbon atoms to fatty alcohols. Thus, we propose that Waterproof plays a key role in tracheal gas filling by providing very long chain fatty alcohols that serve as potential substrates for wax ester synthesis or related hydrophobic substances that ultimately coat the inner lining of the trachea. The hydrophobicity in turn reduces the tensile strength of the liquid inside the trachea, leading to the formation of a gas bubble, the focal point for subsequent gas filling. Waterproof represents the first enzyme described to date that is necessary for tracheal gas filling without affecting branch morphology. Considering its conservation throughout evolution, Waterproof orthologues may play a similar role in the vertebrate lung.
    Developmental Biology 10/2013; 385(1). DOI:10.1016/j.ydbio.2013.10.022 · 3.55 Impact Factor
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