ARF6 bi-directionally regulates dendritic spine formation depending on neuronal maturation and activity.
doi : 10.1074/jbc.M114.634527
Yoonju Kim, Sang-Eun Lee, Joohyun Park, Minhyung Kim, Boyoon Lee, Daehee Hwang and Sunghoe Chang
Recent studies reported conflicting results regarding the role of ARF6 in dendritic spine development but no clear answer for the controversy has been suggested. We found that ARF6 either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increases the spine formation in developing neurons while it decreasing spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite expression patterns of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via phospholipase D pathway is the coincident factor in both stages but antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using TTX or enhancing the activity in mature neurons using PTX or chemical-LTP reverses the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons.
Keywords : ADP ribosylation factor (ARF); ARF6; Phospholipase D; Rac1; Ras-related C3 botulinum toxin substrate 1 (Rac1); dendritic spine; neuronal activity; synaptic plasticity