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

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Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension. / Dahlgaard, Katja; Jung, Anita; Qvortrup, Klaus; Clausen, Henrik; Kjaerulff, Ole; Wandall, Hans H.

In: Proceedings of the National Academy of Sciences USA (PNAS), Vol. 109, No. 18, 2012, p. 6987-92.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Dahlgaard, K, Jung, A, Qvortrup, K, Clausen, H, Kjaerulff, O & Wandall, HH 2012, 'Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension', Proceedings of the National Academy of Sciences USA (PNAS), vol. 109, no. 18, pp. 6987-92. https://doi.org/10.1073/pnas.1115453109

APA

Dahlgaard, K., Jung, A., Qvortrup, K., Clausen, H., Kjaerulff, O., & Wandall, H. H. (2012). Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension. Proceedings of the National Academy of Sciences USA (PNAS), 109(18), 6987-92. https://doi.org/10.1073/pnas.1115453109

Vancouver

Dahlgaard K, Jung A, Qvortrup K, Clausen H, Kjaerulff O, Wandall HH. Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension. Proceedings of the National Academy of Sciences USA (PNAS). 2012;109(18):6987-92. https://doi.org/10.1073/pnas.1115453109

Author

Dahlgaard, Katja ; Jung, Anita ; Qvortrup, Klaus ; Clausen, Henrik ; Kjaerulff, Ole ; Wandall, Hans H. / Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension. In: Proceedings of the National Academy of Sciences USA (PNAS). 2012 ; Vol. 109, No. 18. pp. 6987-92.

Bibtex

@article{13e3ac10177741b7842ea4767e90cd8b,
title = "Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension",
abstract = "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.",
author = "Katja Dahlgaard and Anita Jung and Klaus Qvortrup and Henrik Clausen and Ole Kjaerulff and Wandall, {Hans H}",
year = "2012",
doi = "10.1073/pnas.1115453109",
language = "English",
volume = "109",
pages = "6987--92",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "18",

}

RIS

TY - JOUR

T1 - Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension

AU - Dahlgaard, Katja

AU - Jung, Anita

AU - Qvortrup, Klaus

AU - Clausen, Henrik

AU - Kjaerulff, Ole

AU - Wandall, Hans H

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.1115453109

DO - 10.1073/pnas.1115453109

M3 - Journal article

C2 - 22493273

VL - 109

SP - 6987

EP - 6992

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 18

ER -

ID: 38062974