Abstract
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 (γAddC38) 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 γAddC38. Furthermore, γAddC38-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.
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Acknowledgments
We thank Dr. Niamh Cawley for helpful discussions (SCN, NICHD). We thank Dr. Vincent Schram (NICHD Microscopy Imaging Core) for technical support. This research was supported by the Intramural Research Program of the NICHD, NIH. Joshua J. Park has been supported by NICHD K22 and ARRA grants.
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Hong Lou and Joshua J. Park contributed equally to this work.
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Lou, H., Park, J.J., Phillips, A. et al. γ-Adducin Promotes Process Outgrowth and Secretory Protein Exit from the Golgi Apparatus. J Mol Neurosci 49, 1–10 (2013). https://doi.org/10.1007/s12031-012-9827-0
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DOI: https://doi.org/10.1007/s12031-012-9827-0