SNX17 Mediates Dendritic Spine Maturation via p140Cap

Cui, Qiuyan; Liang, Shiqi; Li, Hao; Guo, Yiqing; Lv, Junkai; Wang, Xinyuan; Qin, Pengwei; Xu, Huaxi; Huang, Timothy Y.; Lu, Youming; Tian, Qing; Zhang, Tongmei

doi:10.1007/s12035-023-03620-4

Cited by 3Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersCellular transport and secretion

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SNX17 Mediates Dendritic Spine Maturation via p140Cap

Cui, Qiuyan, Liang, Shiqi, Li, Hao, Guo, Yiqing, Lv, Junkai, Wang, Xinyuan, Qin, Pengwei, Xu, Huaxi, Huang, Timothy Y., Lu, Youming, Tian, Qing, Zhang, Tongmei·2024·Molecular Neurobiology

DOI 10.1007/s12035-023-03620-4

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Abstract

Sorting nexin17 (SNX17) is a member of the sorting nexin family, which plays a crucial role in endosomal trafficking. Previous research has shown that SNX17 is involved in the recycling or degradation of various proteins associated with neurodevelopmental and neurological diseases in cell models. However, the significance of SNX17 in neurological function in the mouse brain has not been thoroughly investigated. In this study, we generated Snx17 knockout mice and observed that the homozygous deletion of Snx17 (Snx17-/-) resulted in lethality. On the other hand, heterozygous mutant mice (Snx17+/-) exhibited anxiety-like behavior with a reduced preference for social novelty. Furthermore, Snx17 haploinsufficiency led to impaired synaptic transmission and reduced maturation of dendritic spines. Through GST pulldown and interactome analysis, we identified the SRC kinase inhibitor, p140Cap, as a potential downstream target of SNX17. We also demonstrated that the interaction between p140Cap and SNX17 is crucial for dendritic spine maturation. Together, this study provides the first in vivo evidence highlighting the important role of SNX17 in maintaining neuronal function, as well as regulating social novelty and anxiety-like behaviors.

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Authors: Cui, Q., Liang, S., Li, H., Guo, Y., Lv, J., Wang, X., Qin, P., Xu, H., Huang, T. Y., Lu, Y., Tian, Q., & Zhang, T.
ORCID: Zhang, Tongmei
Venue: Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2023-09-13
Volume: 61
Issue: 3
Pages: 1346-1362
ISSN: 0893-7648 (ISSN-L)
1559-1182
DOI: 10.1007/s12035-023-03620-4
OpenAlex: W4386718961
Cited by: 3
References: 51
Citations by year: 2025: 3
FWCI: 0.29
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Molecular Neurobiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (31721002, 81920208014, 31930051, 8180113, 32200795)
Natural Science Foundation of Hubei Province (2022CFB608)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords: SNX17, dendritic spine maturation, sorting nexins, endosomal trafficking, Src kinase inhibitor, synaptic transmission, anxiety-like behavior, social novelty preference, haploinsufficiency, protein-protein interaction
MeSH terms: Animals, Carrier Proteins, Homozygote, Sequence Deletion, Protein Transport, Dendritic Spines, Mice, Sorting Nexins

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SNX17 Mediates Dendritic Spine Maturation via p140Cap

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