Sider Penkov

Dresden University of Technology; Dresden, Germany; TU Dresden

Penkov, Sider et al. (2013) International Worm Meeting "Nematoil - a novel secreted lipid that coats the outer surface of the dauer larva of Pristionchus pacificus."

Kurzchalia, Teymuras, Gruner, Margit, Knolker, Hans-Joachim, Penkov, Sider, Ogawa, Akira, Sommer, Ralf, Passler, Ulrike

[International Worm Meeting, 2013]

The dauer larva formed by multiple nematodes is a specialized developmentally arrested stage for survival and dispersal from unfavorable environment. The survival abilities of dauer larvae are determined by their specific morphology, metabolism, and enhanced stress resistance. A major morphological feature of dauer larvae is the remodeled body surface - they are effectively sealed off by a dauer-specific cuticle that restricts the chemical exchange with the environment. Although the dauer formation is genetically well investigated in several nematode models, there is no much information about the chemical means by which dauer larvae resist to the various kinds of environmental stress. We have found that the nematode Pristionchus pacificus synthesizes dauer stage specific lipids that form a hydrophobic film covering the entire outer surface of the animal. Detailed observation showed that the synthesis and the secretion of the lipids are simultaneously executed late in dauer differentiation, shortly preceded by the molt to dauer larva. The hydrophobic film is a complex mixture of several lipids and advanced chemical analysis revealed that its major component is a very long-chain polyunsaturated wax ester that we name Nematoil. The lipid coat alters the surface properties of the animals - they tend to congregate in tight "dauer clumps" consisting of up to hundreds of individuals, which supposedly enhances their impermeability. Thus, P. pacificus dauer larvae have the biochemical means to enhance their stress response by counteracting collectively.

Erkut, Cihan et al. (2013) International Worm Meeting "How to live without water: Molecular strategies of the dauer larva to survive extreme desiccation."

Verbavatz, Jean-Marc, Fahmy, Karim, Erkut, Cihan, Habermann, Bianca, Kurzchalia, Teymuras V, Vasilj, Andrej, Shevchenko, Andrej, Khesbak, Hassan, Vorkel, Daniela, Penkov, Sider, Boland, Sebastian

[International Worm Meeting, 2013]

Terrestrial animals are almost always challenged by severe desiccation. However, many species have evolved ways to survive this by transiting into an ametabolic state known as anhydrobiosis (life without water). Although known for centuries, the molecular mechanisms underlying anhydrobiosis remained poorly understood because of the lack of a good genetic model. Recently, we showed that the Caenorhabditis elegans dauer is an anhydrobiote. It can survive losing almost its entire body water provided that it is first preconditioned at a mild desiccative environment. We showed that during this preparation, worms accumulate a large amount of the disaccharide trehalose. Trehalose-deficient mutants have a dramatically reduced desiccation tolerance because of extensive damage to plasma membranes and membrane-bound organelles. However, it is very unlikely that trehalose is the only factor involved in anhydrobiosis. In search for others, we surveyed the desiccation-induced changes in the transcriptome and proteome of the worm, which revealed that the desiccation response of C. elegans is focused and involves a small number of functional pathways. Mutants of genes in these pathways most of the time exhibited reduced desiccation tolerance. Some of these pathways have been implicated in drought resistance in plants and animals (e.g. ROS and xenobiotic detoxification, heat-shock response and intrinsically disordered protein expression) and some others have not been associated with anhydrobiosis before (e.g. fatty acid desaturation and polyamine biosynthesis). Our data also suggest that sensing the decrease of ambient humidity (hygrosensation) can be associated to the head neurons. A thorough understanding of the anhydrobiotic ability of the worm can shed light on the fundamental properties of metabolism as well as the material properties of the cell.

Boland, Sebastian et al. (2017) International Worm Meeting "PEGCs: novel glycosphingolipids that mobilize cholesterol in Caenorhabditis elegans."

Boland, Sebastian, Sampaio, Julio, L., Zagoriy, Vyacheslav, Fritsche, Raphael, Reimann, Jakob, Lubken, Tilo, Knolker, Hans-Joachim, Penkov, Sider, Czerwonka, Regina, Schmidt, Ulrike, Kurzchalia, Teymuras, V.

[International Worm Meeting, 2017]

Caenorhabditis elegans (C. elegans) cannot synthesize cholesterol de novo, and requires exogenous cholesterol to progress through its four larval stages. Previously, we showed that worms grown for 2 generations in the absence of cholesterol arrest early in development. This suggests that maternal contributions of sterols are exploitable only in the first generation, but sterol reservoirs are either depleted or inaccessible by the second generation. Here, we present a novel class of phosphorylated glycosphingolipids, which we coined phosphoethanolamine glucosylceramides (PEGCs), that can overcome the sterol deprivation-induced larval arrest. However, they are not direct substitutes for cholesterol because they rescue larval arrest in only one additional generation. Instead, we propose a new model where larval arrest in the second generation of continious sterol deprivation is due not to depletion of internal reservoirs, but a failure to mobilize those reservoirs for promoting growth/development through PEGCs-induced mobilization of internal sterol pools. More precisely, we found that NPC1 and DAF-7 mutants, which display a Daf-c phenotype due to an impaired sterol transport to places of DA synthesis, are rescued by feeding PEGC. Moreover, the biosynthesis of PEGC depends on functional NPC1 and TGF- beta , indicating that these proteins control larval development at least partly through promoting increases in PEGC. Furthermore, glucosylceramide deficiency dramatically reduced PEGC amounts; however, the resulting developmental arrest could be rescued by over-saturation of food with cholesterol. This indicates that PEGC is a major regulator of cholesterol utilization in C. elegans and, thus, of development. The remarkable similarity in sterol trafficking between C. elegans and other metazoans, including mammals, suggests PEGCs might be conserved regulators of sterol transport.