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1.
Mol Psychiatry ; 29(5): 1253-1264, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38228891

RESUMO

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.


Assuntos
Transtorno do Espectro Autista , Modelos Animais de Doenças , Proteínas de Membrana , Transtornos do Neurodesenvolvimento , Animais , Camundongos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Masculino , Neurônios/metabolismo , Comportamento Animal/fisiologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Camundongos Knockout , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Camundongos Endogâmicos C57BL , Comportamento Social , Comportamento Estereotipado , Sinapses/metabolismo , Feminino
2.
FASEB J ; 36(1): e22087, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34888944

RESUMO

Proper dendritic morphology is fundamental to nerve signal transmission; thus, revealing the mechanism by which dendrite arborization is regulated is of great significance. Our previous studies have found that the epigenetic molecule chromodomain Y-like (CDYL) negatively regulates dendritic branching. Current research mostly focuses on the processes downstream of CDYL, whereas the upstream regulatory process has not been investigated to date. In this study, we identified an upstream regulator of CDYL, the E3 ubiquitin ligase tripartite motif-containing protein 32 (TRIM32), which promotes dendrite arborization by mediating the ubiquitylation and degradation of CDYL. By using mass spectrometry and biochemistry strategies, we proved that TRIM32 interacted with CDYL and mediated CDYL ubiquitylation modification in vivo and in vitro. Overexpressing TRIM32 decreased the protein level of CDYL, leading to an increase in the dendritic complexity of primary cultured rat neurons. In contrast, knocking down TRIM32 increased the protein level of CDYL and decreased the dendritic complexity. The truncated form of TRIM32 without E3 ligase activity (ΔRING) lost its ability to regulate dendritic complexity. Most importantly, knockdown of CDYL abolished the reduced complexity of dendrites caused by TRIM32 knockdown, indicating that the TRIM32-mediated regulation of dendritic development depends on its regulation of downstream CDYL. Hence, our findings reveal that TRIM32 could promote dendrite arborization by mediating CDYL degradation. This work initially defines a novel biological role of TRIM32 in regulating mechanisms upstream of CDYL and further presents a potential therapeutic target for the treatment of CDYL-related neurodevelopmental disorders.


Assuntos
Proteínas Correpressoras/metabolismo , Dendritos/metabolismo , Proteólise , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Animais , Proteínas Correpressoras/genética , Dendritos/genética , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética
3.
Antonie Van Leeuwenhoek ; 109(2): 237-51, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26626057

RESUMO

In addition to ammonia-oxidizing bacteria (AOB) the more recently discovered ammonia-oxidizing archaea (AOA) can also oxidize ammonia, but little is known about AOA community structure and abundance in subtropical forest soils. In this study, both AOA and AOB were investigated with molecular techniques in eight types of forests at surface soils (0-2 cm) and deep layers (18-20 cm) in Nanling National Nature Reserve in subtropical China. The results showed that the forest soils, all acidic (pH 4.24-5.10), harbored a wide range of AOA phylotypes, including the genera Nitrosotalea, Nitrososphaera, and another 6 clusters, one of which was reported for the first time. For AOB, only members of Nitrosospira were retrieved. Moreover, the abundance of the ammonia monooxygenase gene (amoA) from AOA dominated over AOB in most soil samples (13/16). Soil depth, rather than forest type, was an important factor shaping the community structure of AOA and AOB. The distribution patterns of AOA and AOB in soil layers were reversed: AOA diversity and abundances in the deep layers were higher than those in the surface layers; on the contrary, AOB diversity and abundances in the deep layers were lower than those in the surface layers. Interestingly, the diversity of AOA was positively correlated with pH, but negatively correlated with organic carbon, total nitrogen and total phosphorus, and the abundance of AOA was negatively correlated with available phosphorus. Our results demonstrated that AOA and AOB were differentially distributed in acidic soils in subtropical forests and affected differently by soil characteristics.


Assuntos
Amônia/metabolismo , Archaea/isolamento & purificação , Archaea/metabolismo , Bactérias/isolamento & purificação , Bactérias/metabolismo , Microbiologia do Solo , Archaea/classificação , Archaea/genética , Bactérias/classificação , Bactérias/genética , China , Conservação dos Recursos Naturais , Dados de Sequência Molecular , Oxirredução , Filogenia , Solo/química
4.
Zootaxa ; 4329(5): 449-462, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-29242463

RESUMO

Material of the genus Domene Fauvel, 1873 from the Chinese provinces Heilongjiang, Anhui, Zhejiang, Fujian, Guizhou, Sichuan, Shaanxi, Yunnan, Guangdong and Guangxi was examined. Twelve species were identified, seven of them described previously, and five are newly described: D. aqiang Peng and Li, sp. n. (Guangdong: Nanling); D. jiangi Peng and Li, sp. n. (Fujian: Tanshan Park); D. jini Peng and Li, sp. n. (Guangxi: Jiuwan Shan); D. nanlingensis Peng and Li, sp. n. (Guangdong: Nanling); D. tui Peng and Li, sp. n. (Guizhou: Sanchahe). The genus is now represented in mainland China by 21 species. A key to the Domene species of mainland China is provided.


Assuntos
Besouros , Distribuição Animal , Estruturas Animais , Animais , China
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