EFA6A是Arf6的一种交换因子,它调控PC12细胞中依赖于NGF的TrkA从早期内体循环和神经元生长。

IF 3.6 3区 生物学 Q3 CELL BIOLOGY
Traffic Pub Date : 2024-05-01 DOI:10.1111/tra.12936
Masahiro Fukaya, Kanta Ibuchi, Takeyuki Sugawara, Makoto Itakura, Akiko Ito, Tomoko Shiroshima, Yoshinobu Hara, Hirotsugu Okamoto, Frédéric Luton, Hiroyuki Sakagami
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引用次数: 0

摘要

TrkA 的内质体转运是神经生长因子(NGF)依赖性神经细胞存活和分化的关键过程。小 GTPase ADP-ribosylation factor 6(Arf6)通过内体转运和肌动蛋白细胞骨架重组参与了 PC12 细胞的 NGF 依赖性过程。然而,Arf6 在 NGF 信号转导中的调控机制尚不清楚。在这项研究中,我们证实了一种 Arf6 特异性鸟嘌呤核苷酸交换因子 EFA6A 在 PC12 细胞中大量表达,并且敲除 EFA6A 能显著抑制 NGF 依赖性 Arf6 激活、TrkA 从早期内体到细胞表面的再循环、ERK1/2 磷酸化的延长以及神经元的生长。我们还证明,EFA6A 通过其 N 端区域与 TrkA 形成蛋白复合物,从而增强了其对 Arf6 的催化活性。同样,我们也证明了 EFA6A 在培养的背根神经节(DRG)神经元中与 TrkA 形成蛋白复合物。此外,与野生型神经元相比,EFA6A基因敲除小鼠培养的DRG神经元表现出NGF依赖的TrkA迁移紊乱。这些发现首次证明了 EFA6A 是 NGF 依赖性 TrkA 运输和信号转导的关键调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
EFA6A, an Exchange Factor for Arf6, Regulates NGF-Dependent TrkA Recycling From Early Endosomes and Neurite Outgrowth in PC12 Cells.

Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N-terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling.

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来源期刊
Traffic
Traffic 生物-细胞生物学
CiteScore
8.10
自引率
2.20%
发文量
50
审稿时长
2 months
期刊介绍: Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.
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