Evidence map›Paper›PMID 38424048›Full record

ArticleSignal transduction and targeted therapy2024

Contactin-associated protein-like 2 (CNTNAP2) mutations impair the essential α-secretase cleavages, leading to autism-like phenotypes.

Qing Zhang, Mengen Xing, Zhengkai Bao, Lu Xu, Yang Bai, Wanqi Chen, Wenhao Pan, Fang Cai, Qunxian Wang, Shipeng Guo and 6 more

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

Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

11 citing papers in PubMed, 13 citations in OpenAlex.

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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

16 authors at 5 institutions in 2 countries.

Qing Zhang *Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Mengen Xing *Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Zhengkai Bao *Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Lu XuOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.ORCID 0000-0003-3231-041X
Yang BaiOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Wanqi ChenOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Wenhao PanOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Fang CaiOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Qunxian WangChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Shipeng GuoChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Jing ZhangCenter for Medical Genetics, Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, 410078, Hunan, China.
Zhe WangThe National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.ORCID 0000-0003-4255-6763
Yili WuOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Yun ZhangThe National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. zhangyun@xwhosp.org.
Jia-Da LiCenter for Medical Genetics, Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics, Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. lijiada@sklmg.edu.cn.
Weihong SongOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. weihong@wmu.edu.cn.ORCID 0000-0001-9928-889X
Wenzhou Medical University · CNCapital Medical University · CNCentral South University · CNChildren's Hospital of Chongqing Medical University · CNUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations in the Contactin-associated protein-like 2 (CNTNAP2) gene are associated with autism spectrum disorder (ASD), and ectodomain shedding of the CNTNAP2 protein plays a role in its function. However, key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown, and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive. In this report we showed that CNTNAP2 undergoes sequential cleavages by furin, ADAM10/17-dependent α-secretase and presenilin-dependent γ-secretase. We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96, and the main α-cleavage product C79 by ADAM10 is required for the subsequent γ-secretase cleavage to generate CNTNAP2 intracellular domain (CICD). ASD-associated CNTNAP2 mutations impair the α-cleavage to generate C79, and the inhibition leads to ASD-like repetitive and social behavior abnormalities in the Cntnap2

Indexed as

Autism Spectrum DisorderAutistic DisorderAmyloid Precursor Protein SecretasesAnimalsContactinsMembrane ProteinsMiceMice, KnockoutMutationNerve Tissue ProteinsPhenotypeAmyloid Precursor Protein SecretasesCNTNAP2 protein, mouseContactinsMembrane ProteinsNerve Tissue Proteins

Identifiers

PMID38424048
PMCPMC10904759
OpenAlexW4392477241

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.