16p11.2 CNV gene Doc2α functions in neurodevelopment and social behaviors through interaction with Secretagogin.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
25 07 2023
Historique:
received: 12 10 2022
revised: 22 04 2023
accepted: 08 06 2023
medline: 31 7 2023
pubmed: 24 6 2023
entrez: 24 6 2023
Statut: ppublish

Résumé

Copy-number variations (CNVs) of the human 16p11.2 genetic locus are associated with neurodevelopmental disorders, including autism spectrum disorders (ASDs) and schizophrenia. However, it remains largely unclear how this locus is involved in the disease pathogenesis. Doc2α is localized within this locus. Here, using in vivo and ex vivo electrophysiological and morphological approaches, we show that Doc2α-deficient mice have neuronal morphological abnormalities and defects in neural activity. Moreover, the Doc2α-deficient mice exhibit social and repetitive behavioral deficits. Furthermore, we demonstrate that Doc2α functions in behavioral and neural phenotypes through interaction with Secretagogin (SCGN). Finally, we demonstrate that SCGN functions in social/repetitive behaviors, glutamate release, and neuronal morphology of the mice through its Doc2α-interacting activity. Therefore, Doc2α likely contributes to neurodevelopmental disorders through its interaction with SCGN.

Identifiants

pubmed: 37354460
pii: S2211-1247(23)00702-7
doi: 10.1016/j.celrep.2023.112691
pii:
doi:

Substances chimiques

Secretagogins 0
Doc2a protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112691

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Qiu-Wen Wang (QW)

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Junhong Qin (J)

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.

Yan-Fen Chen (YF)

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Yingfeng Tu (Y)

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.

Yun-Yun Xing (YY)

Jiangsu Key Laboratory of Language and Cognitive Neuroscience, School of Linguistic Sciences and Arts, Jiangsu Normal University, Xuzhou 221116, China; Jiangsu Collaborative Innovation Center for Language Ability, Xuzhou 221009, China.

Yuchen Wang (Y)

School of Engineering Medicine and School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.

Lv-Yu Yang (LY)

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Si-Yao Lu (SY)

Jiangsu Key Laboratory of Language and Cognitive Neuroscience, School of Linguistic Sciences and Arts, Jiangsu Normal University, Xuzhou 221116, China; Jiangsu Collaborative Innovation Center for Language Ability, Xuzhou 221009, China.

Libo Geng (L)

Jiangsu Key Laboratory of Language and Cognitive Neuroscience, School of Linguistic Sciences and Arts, Jiangsu Normal University, Xuzhou 221116, China; Jiangsu Collaborative Innovation Center for Language Ability, Xuzhou 221009, China.

Wei Shi (W)

School of Engineering Medicine and School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China. Electronic address: shiweilab@buaa.edu.cn.

Yiming Yang (Y)

Jiangsu Key Laboratory of Language and Cognitive Neuroscience, School of Linguistic Sciences and Arts, Jiangsu Normal University, Xuzhou 221116, China; Jiangsu Collaborative Innovation Center for Language Ability, Xuzhou 221009, China. Electronic address: yangym@jsnu.edu.cn.

Jun Yao (J)

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: jyao@mail.tsinghua.edu.cn.

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Classifications MeSH