ARHGEF39, a Gene Implicated in Developmental Language Disorder, Activates RHOA and Is Involved in Cell De-Adhesion and Neural Progenitor Cell Proliferation.
ARHGEF39, a Gene Implicated in Developmental Language Disorder, Activates RHOA and Is Involved in Cell De-Adhesion and Neural Progenitor Cell Proliferation.
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DOI：
10.3389/fnmol.2022.941494
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发表时间：
2022
影响因子：
4.8
通讯作者：
Vernes, Sonja C.
中科院分区：
文献类型：
--
作者：
Anijs, Midas;Devanna, Paolo;Vernes, Sonja C.
ARHGEF39先前通过功能多态性参与发育性语言障碍（DLD），该功能多态性可以破坏microRNA的转录后调控。ARHGEF 39是Rho鸟嘌呤核苷酸交换因子（RhoGEF）家族的一部分，其激活小Rho GTP酶以调节多种细胞过程。然而，人们对ARHGEF39的功能知之甚少，也不知道它的功能如何影响神经发育或相关疾病。在这里，我们探索了ARHGEF 39的分子功能，并表明它激活了Rho GTdR RHOA，并且在细胞培养物中的高ARHGEF 39表达导致脱落细胞的增加。为了探索其在神经发育中的作用，我们分析了已发表的单细胞RNA测序数据，并证明ARHGEF 39是增殖神经祖细胞的标记基因，并且与参与细胞分裂的基因共表达。这表明ARHGEF 39在发育中的大脑中的神经发生中的作用。ARHGEF 39与其他RHOA调节基因的共表达支持RHOA作为ARHGEF 39在神经细胞中的底物，并且RHOA在神经精神障碍中的参与突出了ARHGEF 39与神经发育和障碍之间的潜在联系。了解GT3底物、共表达网络和ARHGEF39下游过程为探索ARHGEF39表达水平改变可能促进神经发育和相关疾病的机制提供了新的途径。
ARHGEF39 was previously implicated in developmental language disorder (DLD) via a functional polymorphism that can disrupt post-transcriptional regulation by microRNAs. ARHGEF39 is part of the family of Rho guanine nucleotide exchange factors (RhoGEFs) that activate small Rho GTPases to regulate a wide variety of cellular processes. However, little is known about the function of ARHGEF39, or how its function might contribute to neurodevelopment or related disorders. Here, we explore the molecular function of ARHGEF39 and show that it activates the Rho GTPase RHOA and that high ARHGEF39 expression in cell cultures leads to an increase of detached cells. To explore its role in neurodevelopment, we analyse published single cell RNA-sequencing data and demonstrate that ARHGEF39 is a marker gene for proliferating neural progenitor cells and that it is co-expressed with genes involved in cell division. This suggests a role for ARHGEF39 in neurogenesis in the developing brain. The co-expression of ARHGEF39 with other RHOA-regulating genes supports RHOA as substrate of ARHGEF39 in neural cells, and the involvement of RHOA in neuropsychiatric disorders highlights a potential link between ARHGEF39 and neurodevelopment and disorder. Understanding the GTPase substrate, co-expression network, and processes downstream of ARHGEF39 provide new avenues for exploring the mechanisms by which altered expression levels of ARHGEF39 may contribute to neurodevelopment and associated disorders.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1083/jcb.200207130
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
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通讯作者：
Spiro, John E.
DOI：
10.1083/jcb.201204107
发表时间：
2012-09-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Barr FA
影响因子：
11
作者：
Devanna P;Chen XS;Ho J;Gajewski D;Smith SD;Gialluisi A;Francks C;Fisher SE;Newbury DF;Vernes SC
通讯作者：
Vernes SC