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β-PIX-d是ARHGEF7鸟嘌呤核苷酸交换因子家族的成员之一,可激活Rac1并诱导原代皮质神经元的神经突生成。

β-PIX-d, a Member of the ARHGEF7 Guanine Nucleotide Exchange Factor Family, Activates Rac1 and Induces Neuritogenesis in Primary Cortical Neurons.

作者信息

Kim Seunghyuk, Park Heeyoung, Kang Jieun, Choi Seunghyuk, Sadra Ali, Huh Sung-Oh

机构信息

Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 24252, Korea.

出版信息

Exp Neurobiol. 2024 Oct 31;33(5):215-224. doi: 10.5607/en24026.

Abstract

β-PIX, a Rac1/Cdc42-specific guanine nucleotide exchange factor, is known to regulate actin cytoskeleton remodeling during cell migration. In this study, we investigated the effects of β-PIX-d, an isoform of β-PIX, on neocortical development and neuritogenesis. Overexpression of β-PIX-d in the embryonic neocortex induced increased cell clusters and enhanced neurite outgrowth in cortical neurons. Following in utero electroporation of β-PIX-d expression vectors into neuronal progenitor cells at embryonic day 13.5 (E13.5), histological analysis at postnatal day 0 (P0) revealed the presence of clustered neurons and neurites outside of the marginal zone (MZ). Immunofluorescence staining with the neuronal marker TuJ1 confirmed that the clustered structures were predominantly composed of neurons. Layer-specific marker analysis further demonstrated the misplacement of layer V-VI neurons into layer I and the subarachnoid space. In primary neocortical cultures, β-PIX-d overexpression promoted neuritogenesis and increased Rac1 activity, as detected by pull-down assays. These findings suggest that β-PIX-d and Rac1 interactions play a critical role in the formation of neocortical clustering and the regulation of neuritogenesis.

摘要

β-PIX是一种Rac1/Cdc42特异性鸟嘌呤核苷酸交换因子,已知其在细胞迁移过程中调节肌动蛋白细胞骨架重塑。在本研究中,我们研究了β-PIX的一种同工型β-PIX-d对新皮质发育和神经突发生的影响。在胚胎新皮质中过表达β-PIX-d会导致细胞簇增加,并增强皮质神经元的神经突生长。在胚胎第13.5天(E13.5)将β-PIX-d表达载体子宫内电穿孔导入神经元祖细胞后,出生后第0天(P0)的组织学分析显示,在边缘区(MZ)外存在聚集的神经元和神经突。用神经元标记物TuJ1进行免疫荧光染色证实,聚集结构主要由神经元组成。层特异性标记分析进一步证明V-VI层神经元错位到I层和蛛网膜下腔。在原代新皮质培养物中,通过下拉试验检测到,β-PIX-d过表达促进了神经突发生并增加了Rac1活性。这些发现表明,β-PIX-d与Rac1的相互作用在新皮质聚集的形成和神经突发生的调节中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/11581827/1de8939c1cbe/en-33-5-215-f1.jpg

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