Drosophila egghead Encodes a β1,4-Mannosyltransferase Predicted to Form the Immediate Precursor Glycosphingolipid Substrate for brainiac

Wandall, Hans H.; Pedersen, Jacob; Park, Chaeho; Levery, Steven B.; Pizette, Sandrine; Cohen, Stephen M.; Schwientek, Tilo; Clausen, Henrik

doi:10.1074/jbc.c200619200

Cited by 61 publications

(50 citation statements)

References 32 publications

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“…We previously identified Egghead (Egh) and Brainiac (Brn) as glycosyltransferases responsible for GSL biosynthesis in Drosophila, catalyzing the addition of the second and third glycosyl residues of the GSL core oligosaccharide chain, respectively (Fig. 1A) (1,2,8). We also showed that egh and brn mutants are devoid of elongated GSLs, demonstrating that these genes are key regulators of GSL biosynthesis (2).…”

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confidence: 72%

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Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension

Dahlgaard¹,

Jung

Qvortrup

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Glycosphingolipids (GSLs) are of fundamental importance in the nervous system. However, the molecular details associated with GSL function are largely unknown, in part because of the complexity of GSL biosynthesis in vertebrates. In Drosophila , only one major GSL biosynthetic pathway exists, controlled by the glycosyltransferase Egghead (Egh). Here we discovered that loss of Egh causes overgrowth of peripheral nerves and attraction of immune cells to the nerves. This phenotype is reminiscent of the human disorder neurofibromatosis type 1, which is characterized by disfiguring nerve sheath tumors with mast cell infiltration, increased cancer risk, and learning deficits. Neurofibromatosis type 1 is due to a reduction of the tumor suppressor neurofibromin, a negative regulator of the small GTPase Ras. Enhanced Ras signaling promotes glial growth through activation of phosphatidylinositol 3-kinase (PI3K) and its downstream kinase Akt. We find that overgrowth of peripheral nerves in egh mutants is suppressed by down-regulation of the PI3K signaling pathway by expression of either dominant-negative PI3K, the tumor suppressor PTEN, or the transcription factor FOXO in the subperineurial glia. These results show that loss of the glycosyltransferase Egh affects membrane signaling and activation of PI3K signaling in glia of the peripheral nervous system, and suggest that glycosyltransferases may suppress proliferation.

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confidence: 72%

“…In Drosophila, extension of glucosylceramide (GlcCer) is exclusively controlled by the mannosyltransferase Egh (Fig. 1A) (2,8). In third instar larvae, we found that loss of egh was often associated with enlargement of the peripheral nerves ( Fig.…”

Section: Egh Mutants Exhibit Enlargement Of Peripheral Nerves With Atmentioning

confidence: 82%

Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension

Dahlgaard¹,

Jung

Qvortrup

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Our analysis showed that a specific locus, egh, is needed for robust male courtship behavior (Figure 4). egh encodes a 1,4-mannosyltransferase that regulates glycosphingolipid biosynthesis (Wandall et al 2003), affects Drosophila neural development and behavior, and is required in Ap neurons for female Sex-peptide response post mating (Soller et al 2006). Since ap md544 -Gal4 (a Gal4 insertion in ap) is expressed in the adult nervous system of both sexes ( Figure S2), we examined whether this neural circuit also functioned in males to regulate courtship behavior.…”

Section: Discussionmentioning

confidence: 99%

Socially-Responsive Gene Expression in MaleDrosophila melanogasterIs Influenced by the Sex of the Interacting Partner

Ellis¹,

Carney

2011

Genetics

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Behavior is influenced by an organism's genes and environment, including its interactions with same or opposite sex individuals. Drosophila melanogaster perform innate, yet socially modifiable, courtship behaviors that are sex specific and require rapid integration and response to multiple sensory cues. Furthermore, males must recognize and distinguish other males from female courtship objects. It is likely that perception, integration, and response to sex-specific cues is partially mediated by changes in gene expression. Reasoning that social interactions with members of either sex would impact gene expression, we compared expression profiles in heads of males that courted females, males that interacted with other males, or males that did not interact with another fly. Expression of 281 loci changes when males interact with females, whereas 505 changes occur in response to male-male interactions. Of these genes, 265 are responsive to encounters with either sex and 240 respond specifically to male-male interactions. Interestingly, 16 genes change expression only when a male courts a female, suggesting that these changes are a specific response to male-female courtship interactions. We supported our hypothesis that sociallyresponsive genes can function in behavior by showing that egghead (egh) expression, which increases during social interactions, is required for robust male-to-female courtship. We predict that analyzing additional socially-responsive genes will give us insight into genes and neural signaling pathways that influence reproductive and other behavioral interactions.

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“…One of the main experimental difficulties in determining the catalytic function of GTs relates to the limited availability of relevant candidate oligosaccharide acceptors. However, the range of possible acceptor structures can be narrowed down by exploiting the observation that monosaccharides can serve as acceptor analogs if provided at high concentrations in the GT assay, also denoted as the free sugar assay (Brü ckner et al, 2000;Wandall et al, 2003). …”

Section: Rgxt1 and Rgxt2 Expressed In Baculovirus-transfected Insect mentioning

confidence: 99%

Arabidopsis thaliana RGXT1 and RGXT2 Encode Golgi-Localized (1,3)-α-d-Xylosyltransferases Involved in the Synthesis of Pectic Rhamnogalacturonan-II

Egelund¹,

Petersen²,

Motawia³

et al. 2006

The Plant Cell

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126

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Two homologous plant-specific Arabidopsis thaliana genes, RGXT1 and RGXT2, belong to a new family of glycosyltransferases (CAZy GT-family-77) and encode cell wall (1,3)-a-D-xylosyltransferases. The deduced amino acid sequences contain single transmembrane domains near the N terminus, indicative of a type II membrane protein structure. Soluble secreted forms of the corresponding proteins expressed in insect cells showed xylosyltransferase activity, transferring D-xylose from UDPa-D-xylose to L-fucose. The disaccharide product was hydrolyzed by a-xylosidase, whereas no reaction was catalyzed by b-xylosidase. Furthermore, the regio-and stereochemistry of the methyl xylosyl-fucoside was determined by nuclear magnetic resonance to be an a-(1,3) linkage, demonstrating the isolated glycosyltransferases to be (1,3)-a-D-xylosyltransferases. This particular linkage is only known in rhamnogalacturonan-II, a complex polysaccharide essential to vascular plants, and is conserved across higher plant families. Rhamnogalacturonan-II isolated from both RGXT1 and RGXT2 T-DNA insertional mutants functioned as specific acceptor molecules in the xylosyltransferase assay. Expression of RGXT1-and RGXT2-enhanced green fluorescent protein constructs in Arabidopsis revealed that both fusion proteins were targeted to a Brefeldin A-sensitive compartment and also colocalized with the Golgi marker dye BODIPY TR ceramide, consistent with targeting to the Golgi apparatus. Taken together, these results suggest that RGXT1 and RGXT2 encode Golgi-localized (1,3)-a-D-xylosyltransferases involved in the biosynthesis of pectic rhamnogalacturonan-II.

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Drosophila egghead Encodes a β1,4-Mannosyltransferase Predicted to Form the Immediate Precursor Glycosphingolipid Substrate for brainiac

Cited by 61 publications

References 32 publications

Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension

Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension

Socially-Responsive Gene Expression in MaleDrosophila melanogasterIs Influenced by the Sex of the Interacting Partner

Arabidopsis thaliana RGXT1 and RGXT2 Encode Golgi-Localized (1,3)-α-d-Xylosyltransferases Involved in the Synthesis of Pectic Rhamnogalacturonan-II

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