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

Result code in 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>
Alternative codes found
RIV/61388963:_____/18:00489690 RIV/00064165:_____/18:10376458
Result on the web
<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>

Result language
angličtina
Original language name
Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection
Original language description
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's cytoprotection.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GA15-06582S" target="_blank" >GA15-06582S: Molecular mechanisms of relapsed acute lymphoblastic leukemia: characterization of hyperactive mutants of cytosolic purine 5´-nucleotidase</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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