Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376458" target="_blank" >RIV/00216208:11110/18:10376458 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/18:00489690 RIV/00064165:_____/18:10376458

Výsledek na webu

<a href="https://doi.org/10.1038/s41467-018-03355-0" target="_blank" >https://doi.org/10.1038/s41467-018-03355-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-018-03355-0" target="_blank" >10.1038/s41467-018-03355-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection

Popis výsledku v původním jazyce

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protects dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A. 23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANF&apos;s cytoprotection.

Název v anglickém jazyce

Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection

Popis výsledku anglicky

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protects dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A. 23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANF&apos;s cytoprotection.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA15-06582S" target="_blank" >GA15-06582S: Molekulární mechanismy relapsu akutní lymfoblastické leukemie: charakterizace hyperaktivních mutantů cytosolické purinové 5´-nukleotidasy</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications [online]

ISSN

2041-1723

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

—

Kód UT WoS článku

000426355700010

EID výsledku v databázi Scopus

2-s2.0-85042869585