Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides

Benjamin Hallier, Ronja Schiemann, Eva Cordes, Jessica Vitos-Faleato, Stefan Walter, Jürgen J Heinisch, Anders Malmendal, Achim Paululat, Heiko Meyer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Insulin and IGF signaling are critical to numerous developmental and physiological processes, with perturbations being pathognomonic of various diseases, including diabetes. Although the functional roles of the respective signaling pathways have been extensively studied, the control of insulin production and release is only partially understood. Herein, we show that in Drosophila expression of insulin-like peptides is regulated by neprilysin activity. Concomitant phenotypes of altered neprilysin expression included impaired food intake, reduced body size, and characteristic changes in the metabolite composition. Ectopic expression of a catalytically inactive mutant did not elicit any of the phenotypes, which confirms abnormal peptide hydrolysis as a causative factor. A screen for corresponding substrates of the neprilysin identified distinct peptides that regulate insulin-like peptide expression, feeding behavior, or both. The high functional conservation of neprilysins and their substrates renders the characterized principles applicable to numerous species, including higher eukaryotes and humans.

OriginalsprogEngelsk
Artikelnummere19430
TidsskrifteLife
Vol/bind5
ISSN2050-084X
DOI
StatusUdgivet - 6 dec. 2016
Udgivet eksterntJa

Citer dette

Hallier, B., Schiemann, R., Cordes, E., Vitos-Faleato, J., Walter, S., Heinisch, J. J., ... Meyer, H. (2016). Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides. eLife, 5, [e19430]. https://doi.org/10.7554/eLife.19430
Hallier, Benjamin ; Schiemann, Ronja ; Cordes, Eva ; Vitos-Faleato, Jessica ; Walter, Stefan ; Heinisch, Jürgen J ; Malmendal, Anders ; Paululat, Achim ; Meyer, Heiko. / Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides. I: eLife. 2016 ; Bind 5.
@article{3bd410874f194ad88c1a5715dcb190b7,
title = "Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides",
abstract = "Insulin and IGF signaling are critical to numerous developmental and physiological processes, with perturbations being pathognomonic of various diseases, including diabetes. Although the functional roles of the respective signaling pathways have been extensively studied, the control of insulin production and release is only partially understood. Herein, we show that in Drosophila expression of insulin-like peptides is regulated by neprilysin activity. Concomitant phenotypes of altered neprilysin expression included impaired food intake, reduced body size, and characteristic changes in the metabolite composition. Ectopic expression of a catalytically inactive mutant did not elicit any of the phenotypes, which confirms abnormal peptide hydrolysis as a causative factor. A screen for corresponding substrates of the neprilysin identified distinct peptides that regulate insulin-like peptide expression, feeding behavior, or both. The high functional conservation of neprilysins and their substrates renders the characterized principles applicable to numerous species, including higher eukaryotes and humans.",
author = "Benjamin Hallier and Ronja Schiemann and Eva Cordes and Jessica Vitos-Faleato and Stefan Walter and Heinisch, {J{\"u}rgen J} and Anders Malmendal and Achim Paululat and Heiko Meyer",
year = "2016",
month = "12",
day = "6",
doi = "10.7554/eLife.19430",
language = "English",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

Hallier, B, Schiemann, R, Cordes, E, Vitos-Faleato, J, Walter, S, Heinisch, JJ, Malmendal, A, Paululat, A & Meyer, H 2016, 'Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides', eLife, bind 5, e19430. https://doi.org/10.7554/eLife.19430

Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides. / Hallier, Benjamin; Schiemann, Ronja; Cordes, Eva; Vitos-Faleato, Jessica; Walter, Stefan; Heinisch, Jürgen J; Malmendal, Anders; Paululat, Achim; Meyer, Heiko.

I: eLife, Bind 5, e19430, 06.12.2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides

AU - Hallier, Benjamin

AU - Schiemann, Ronja

AU - Cordes, Eva

AU - Vitos-Faleato, Jessica

AU - Walter, Stefan

AU - Heinisch, Jürgen J

AU - Malmendal, Anders

AU - Paululat, Achim

AU - Meyer, Heiko

PY - 2016/12/6

Y1 - 2016/12/6

N2 - Insulin and IGF signaling are critical to numerous developmental and physiological processes, with perturbations being pathognomonic of various diseases, including diabetes. Although the functional roles of the respective signaling pathways have been extensively studied, the control of insulin production and release is only partially understood. Herein, we show that in Drosophila expression of insulin-like peptides is regulated by neprilysin activity. Concomitant phenotypes of altered neprilysin expression included impaired food intake, reduced body size, and characteristic changes in the metabolite composition. Ectopic expression of a catalytically inactive mutant did not elicit any of the phenotypes, which confirms abnormal peptide hydrolysis as a causative factor. A screen for corresponding substrates of the neprilysin identified distinct peptides that regulate insulin-like peptide expression, feeding behavior, or both. The high functional conservation of neprilysins and their substrates renders the characterized principles applicable to numerous species, including higher eukaryotes and humans.

AB - Insulin and IGF signaling are critical to numerous developmental and physiological processes, with perturbations being pathognomonic of various diseases, including diabetes. Although the functional roles of the respective signaling pathways have been extensively studied, the control of insulin production and release is only partially understood. Herein, we show that in Drosophila expression of insulin-like peptides is regulated by neprilysin activity. Concomitant phenotypes of altered neprilysin expression included impaired food intake, reduced body size, and characteristic changes in the metabolite composition. Ectopic expression of a catalytically inactive mutant did not elicit any of the phenotypes, which confirms abnormal peptide hydrolysis as a causative factor. A screen for corresponding substrates of the neprilysin identified distinct peptides that regulate insulin-like peptide expression, feeding behavior, or both. The high functional conservation of neprilysins and their substrates renders the characterized principles applicable to numerous species, including higher eukaryotes and humans.

U2 - 10.7554/eLife.19430

DO - 10.7554/eLife.19430

M3 - Journal article

VL - 5

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e19430

ER -

Hallier B, Schiemann R, Cordes E, Vitos-Faleato J, Walter S, Heinisch JJ et al. Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides. eLife. 2016 dec 6;5. e19430. https://doi.org/10.7554/eLife.19430