Evidence map›Paper›PMID 25501601›Full record

ArticleCell death and differentiation2015

The MT2 receptor stimulates axonogenesis and enhances synaptic transmission by activating Akt signaling.

D Liu, N Wei, H-Y Man, Y Lu, L-Q Zhu, J-Z Wang

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

Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

40 citing papers in PubMed, 68 citations in OpenAlex.

  1. Trial
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  5. Epigenetic Regulation of DAPK1 and Netrin-1 Drives Diabetic Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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  8. Sleep deprivation soon after recovery from synthetic torpor enhances tau protein dephosphorylation in the rat brain.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024
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  9. Article
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  11. Article
  12. Article
  13. Article
  14. Melatonin: A Neurotrophic Factor?Molecules (Basel, Switzerland) · 2022
    Review
  15. Review
  16. Review
  17. Review
  18. An Examination of the Putative Role of Melatonin in Exosome Biogenesis.Frontiers in cell and developmental biology · 2021
    Review
  19. Article
  20. Article
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

6 authors at 3 institutions in 3 countries.

D Liu1] Department of Pathophyiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2] Sino-Canada Collaborative Platform on Molecular Biology of Neurological Disease, Key Laboratory of Neurological Diseases, Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3] The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
N Wei1] Department of Pathophyiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2] Sino-Canada Collaborative Platform on Molecular Biology of Neurological Disease, Key Laboratory of Neurological Diseases, Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3] The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
H-Y ManDepartment of Biology, Boston University, Boston, MA 02215, USA.
Y Lu1] Sino-Canada Collaborative Platform on Molecular Biology of Neurological Disease, Key Laboratory of Neurological Diseases, Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2] The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
L-Q Zhu1] Department of Pathophyiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2] Sino-Canada Collaborative Platform on Molecular Biology of Neurological Disease, Key Laboratory of Neurological Diseases, Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3] The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
J-Z Wang1] Department of Pathophyiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2] Sino-Canada Collaborative Platform on Molecular Biology of Neurological Disease, Key Laboratory of Neurological Diseases, Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3] The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
Huazhong University of Science and Technology · CNMinistry of Education and Child Care · CABoston University · US

Funding

Molecular Mechanisms of Homeostatic Synaptic PlasticityR01MH079407 · NIMH · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI MAN, HENGYE · 2008 to 2018
$3.9M
NIMH NIH HHS R01 MH079407
6 · The paper itself

Abstract

The MT2 receptor is a principal type of G protein-coupled receptor that mainly mediates the effects of melatonin. Deficits of melatonin/MT2 signaling have been found in many neurological disorders, including Alzheimer's disease, the most common cause of dementia in the elderly, suggesting that preservation of the MT2 receptor may be beneficial to these neurological disorders. However, direct evidence linking the MT2 receptor to cognition-related synaptic plasticity remains to be established. Here, we report that the MT2 receptor, but not the MT1 receptor, is essential for axonogenesis both in vitro and in vivo. We find that axon formation is retarded in MT2 receptor knockout mice, MT2-shRNA electroporated brain slices or primary neurons treated with an MT2 receptor selective antagonist. Activation of the MT2 receptor promotes axonogenesis that is associated with an enhancement in excitatory synaptic transmission in central neurons. The signaling components downstream of the MT2 receptor consist of the Akt/GSK-3β/CRMP-2 cascade. The MT2 receptor C-terminal motif binds to Akt directly. Either inhibition of the MT2 receptor or disruption of MT2 receptor-Akt binding reduces axonogenesis and synaptic transmission. Our data suggest that the MT2 receptor activates Akt/GSK-3β/CRMP-2 signaling and is necessary and sufficient to mediate functional axonogenesis and synaptic formation in central neurons.

Indexed as

Signal TransductionAnimalsAxonsCells, CulturedFluorescence Recovery After PhotobleachingGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHEK293 CellsHumansIn Vitro TechniquesMelatoninMiceMice, KnockoutNeuronsProto-Oncogene Proteins c-aktRats4-phenyl-2-propionamidotetralineGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanGsk3b protein, mouseGsk3b protein, ratMelatoninProto-Oncogene Proteins c-aktReceptor, Melatonin, MT1Receptor, Melatonin, MT2RNA, Small InterferingTetrahydronaphthalenes

Identifiers

PMID25501601
PMCPMC4356342
OpenAlexW2008612988

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.