Evidence map›Paper›PMID 26720341›Full record

ArticleCell death & disease2015

Role of two sequence motifs of mesencephalic astrocyte-derived neurotrophic factor in its survival-promoting activity.

K Mätlik, Li-ying Yu, A Eesmaa, M Hellman, P Lindholm, J Peränen, E Galli, J Anttila, M Saarma, P Permi and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
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  10. Dual role of neuroplastin in pancreatic β cells: Regulating insulin secretion and promoting islet inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  18. UPR Responsive GenesFrontiers in cellular neuroscience · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

K MätlikProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
Li-ying YuProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
A EesmaaProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
M HellmanProgram in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, PO Box 65, Helsinki 00014, Finland.
P LindholmProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
J PeränenProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
E GalliProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
J AnttilaProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
M SaarmaProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
P PermiProgram in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, PO Box 65, Helsinki 00014, Finland.
M AiravaaraProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
U ArumäeProgram in Developmental Biology, Institute of Biotechnology, University of Helsinki, Viikki Biocenter, PO Box 65, Helsinki 00014, Finland.
Biocenter Finland · FIUniversity of Helsinki · FITallinn University of Technology · EEUniversity of Jyväskylä · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a prosurvival protein that protects the cells when applied intracellularly in vitro or extracellularly in vivo. Its protective mechanisms are poorly known. Here we studied the role of two short sequence motifs within the carboxy-(C) terminal domain of MANF in its neuroprotective activity: the CKGC sequence (a CXXC motif) that could be involved in redox reactions, and the C-terminal RTDL sequence, an endoplasmic reticulum (ER) retention signal. We mutated these motifs and analyzed the antiapoptotic effect and intracellular localization of these mutants of MANF when overexpressed in cultured sympathetic or sensory neurons. As an in vivo model for studying the effect of these mutants after their extracellular application, we used the rat model of cerebral ischemia. Even though we found no evidence for oxidoreductase activity of MANF, the mutation of CXXC motif completely abolished its protective effect, showing that this motif is crucial for both MANF's intracellular and extracellular activity. The RTDL motif was not needed for the neuroprotective activity of MANF after its extracellular application in the stroke model in vivo. However, in vitro the deletion of RTDL motif inactivated MANF in the sympathetic neurons where the mutant protein localized to Golgi, but not in the sensory neurons where the mutant localized to the ER, showing that intracellular MANF protects these peripheral neurons in vitro only when localized to the ER.

Indexed as

Amino Acid MotifsAnimalsCell SurvivalCysteineDisease Models, AnimalEtoposideGanglia, SpinalGolgi ApparatusIntracellular SpaceMiceMutationNerve Growth FactorsNeuroprotective AgentsProtein TransportRats, Sprague-DawleyRecombinant ProteinsCysteineEtoposideMANF protein, humanNerve Growth FactorsNeuroprotective AgentsRecombinant Proteins

Identifiers

PMID26720341
PMCPMC4720903
OpenAlexW2220739258

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.