Evidence map›Paper›PMID 38747058›Full record

ArticleZoological research2024

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton, modulating emotional behavior.

Laidong Yu, Fangfang Zeng, Mengshu Fan, Kexuan Zhang, Jingjing Duan, Yalu Tan, Panlin Liao, Jin Wen, Chenyu Wang, Meilin Wang and 7 more

Abstract read
In one paragraph

Article in Zoological research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

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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

17 authors.

Laidong YuHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Fangfang ZengHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Mengshu FanHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Kexuan ZhangHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Jingjing DuanHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Yalu TanHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Panlin LiaoHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Jin WenHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Chenyu WangHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Meilin WangHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Jialong YuanHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Xinxin PangHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Yan HuangHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Yangzhou ZhangHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Jia-Da LiCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410008, China.
Zhuohua ZhangHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Zhonghua HuHunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Funding

FACTORS THAT MODIFY INSULIN ACTIONR01DK002001 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BUSE, MARIA G · 1986 to 2012
$3.1M
Factors that modify insulin actionR56DK002001 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BUSE, MARIA G · 2008 to 2008
$199k
NIDDK NIH HHS R01 DK002001NIDDK NIH HHS R56 DK002001
6 · The paper itself

Abstract

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function. Synaptic abnormalities, such as defects in the density and morphology of postsynaptic dendritic spines, underlie the pathology of various neuropsychiatric disorders. Protocadherin 17 (PCDH17) is associated with major mood disorders, including bipolar disorder and depression. However, the molecular mechanisms by which PCDH17 regulates spine number, morphology, and behavior remain elusive. In this study, we found that PCDH17 functions at postsynaptic sites, restricting the number and size of dendritic spines in excitatory neurons. Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety- and depression-like behaviors in mice. Mechanistically, PCDH17 interacts with actin-relevant proteins and regulates actin filament (F-actin) organization. Specifically, PCDH17 binds to ROCK2, increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3 (Ser3). Inhibition of ROCK2 activity with belumosudil (KD025) ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression, suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development. Hence, these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior, providing pathological insights into the neurobiological basis of mood disorders.

Indexed as

Actin CytoskeletonCadherinsDendritic SpinesProtocadherinsrho-Associated KinasesAnimalsGene Expression RegulationMiceCadherinsPcdh17 protein, mouseProtocadherinsrho-Associated KinasesActin cytoskeletonAnimal behaviorDendritic spineMood disorderSynapse development

Identifiers

PMID38747058
PMCPMC11188600

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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.