Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.

Disturbances in the homeostasis of endoplasmic reticulum (ER) referred to as ER stress is involved in a variety of human diseases. ER stress activates unfolded protein response (UPR), a cellular mechanism the purpose of which is to restore ER homeostasis. Previous studies show that Mesencephalic Ast...

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Main Authors: Riitta Lindström, Päivi Lindholm, Jukka Kallijärvi, Mari Palgi, Mart Saarma, Tapio I Heino
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0151550&type=printable
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author Riitta Lindström
Päivi Lindholm
Jukka Kallijärvi
Mari Palgi
Mart Saarma
Tapio I Heino
author_facet Riitta Lindström
Päivi Lindholm
Jukka Kallijärvi
Mari Palgi
Mart Saarma
Tapio I Heino
author_sort Riitta Lindström
collection DOAJ
description Disturbances in the homeostasis of endoplasmic reticulum (ER) referred to as ER stress is involved in a variety of human diseases. ER stress activates unfolded protein response (UPR), a cellular mechanism the purpose of which is to restore ER homeostasis. Previous studies show that Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) is an important novel component in the regulation of UPR. In vertebrates, MANF is upregulated by ER stress and protects cells against ER stress-induced cell death. Biochemical studies have revealed an interaction between mammalian MANF and GRP78, the major ER chaperone promoting protein folding. In this study we discovered that the upregulation of MANF expression in response to drug-induced ER stress is conserved between Drosophila and mammals. Additionally, by using a genetic in vivo approach we found genetic interactions between Drosophila Manf and genes encoding for Drosophila homologues of GRP78, PERK and XBP1, the key components of UPR. Our data suggest a role for Manf in the regulation of Drosophila UPR.
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spelling doaj.art-1585ec2f73444f0199f73aa3738bccdb2025-02-25T05:34:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015155010.1371/journal.pone.0151550Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.Riitta LindströmPäivi LindholmJukka KallijärviMari PalgiMart SaarmaTapio I HeinoDisturbances in the homeostasis of endoplasmic reticulum (ER) referred to as ER stress is involved in a variety of human diseases. ER stress activates unfolded protein response (UPR), a cellular mechanism the purpose of which is to restore ER homeostasis. Previous studies show that Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) is an important novel component in the regulation of UPR. In vertebrates, MANF is upregulated by ER stress and protects cells against ER stress-induced cell death. Biochemical studies have revealed an interaction between mammalian MANF and GRP78, the major ER chaperone promoting protein folding. In this study we discovered that the upregulation of MANF expression in response to drug-induced ER stress is conserved between Drosophila and mammals. Additionally, by using a genetic in vivo approach we found genetic interactions between Drosophila Manf and genes encoding for Drosophila homologues of GRP78, PERK and XBP1, the key components of UPR. Our data suggest a role for Manf in the regulation of Drosophila UPR.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0151550&type=printable
spellingShingle Riitta Lindström
Päivi Lindholm
Jukka Kallijärvi
Mari Palgi
Mart Saarma
Tapio I Heino
Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.
PLoS ONE
title Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.
title_full Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.
title_fullStr Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.
title_full_unstemmed Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.
title_short Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.
title_sort exploring the conserved role of manf in the unfolded protein response in drosophila melanogaster
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0151550&type=printable
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