Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bldg 49, Rm 5A22, 49 Convent Drive, Bethesda, MD 20892, USA.
J Mol Neurosci. 2013 Jan;49(1):1-10. doi: 10.1007/s12031-012-9827-0. Epub 2012 Jun 17.
α, β, and γ adducins mediate F-actin remodeling of plasma membrane structures as heterotetramers. Here, we present two new functions of γ-adducin. (1) Overexpression of γ-adducin promoted formation of neurite-like processes in non-neuronal fibroblast COS7 cells. Conversely, overexpression of the C-terminal 38 amino acids of γ-adducin (γAdd(C38)) acting as a dominant negative inhibited formation of neurites/processes in Neuro2A cells and anterior pituitary AtT20 cells. (2) γ-Adducin appears to facilitate pro-opiomelanocortin (POMC) exit from the trans-Golgi network (TGN) by re-organizing the actin network around the Golgi complex. Filamentous actins (F-actins) which formed puncti around the Golgi complex in control cells were dispersed in AtT20 cells stably transfected with γAdd(C38). Furthermore, γAdd(C38)-transfectants showed significant accumulation of POMC/adrenocorticotropin (ACTH) in the Golgi complex and diminished POMC/ACTH vesicles in the cell processes. The C-terminal 38 amino acids of γ-adducin interacted with F-actins around the Golgi complex, to facilitate F-actin-mediated budding of POMC/ACTH vesicles from the TGN. Thus, we propose that γ-adducin, via its interaction with F-actins, plays a critical role in actin remodeling to facilitate process/neurite outgrowth, as well as budding of POMC/ACTH vesicles from the TGN via its interaction with peri-Golgi F-actins.
α、β 和 γ 辅肌动蛋白作为异四聚体介导质膜结构的 F-肌动蛋白重塑。在这里,我们提出了 γ 辅肌动蛋白的两个新功能。(1)γ 辅肌动蛋白的过表达促进了非神经元成纤维细胞 COS7 细胞中神经突样过程的形成。相反,作为显性负性的 γ 辅肌动蛋白的 C 端 38 个氨基酸(γAdd(C38))的过表达抑制了 Neuro2A 细胞和垂体前叶 AtT20 细胞中神经突/过程的形成。(2)γ 辅肌动蛋白似乎通过重新组织高尔基体周围的肌动蛋白网络,促进 pro-opiomelanocortin (POMC) 从反式高尔基体网络 (TGN) 中输出。在对照细胞中,在高尔基体周围形成点状的丝状肌动蛋白 (F-肌动蛋白) 在稳定转染 γAdd(C38)的 AtT20 细胞中被分散。此外,γAdd(C38)转染细胞在高尔基体中显示出 POMC/促肾上腺皮质激素 (ACTH) 的明显积累,并在细胞过程中减少 POMC/ACTH 囊泡。γ 辅肌动蛋白的 C 端 38 个氨基酸与高尔基体周围的 F-肌动蛋白相互作用,促进 F-肌动蛋白介导的 POMC/ACTH 囊泡从 TGN 的出芽。因此,我们提出 γ 辅肌动蛋白通过与 F-肌动蛋白相互作用,在肌动蛋白重塑中发挥关键作用,以促进突起/神经突的生长,以及通过与周高尔基体 F-肌动蛋白相互作用促进 POMC/ACTH 囊泡从 TGN 的出芽。