A new signalsome containing cytohesin-2 and CCDC120 controls neurite outgrowth

Many functions in the nervous system depend on neural morphological changes including the cell polarity and neurite outgrowth and propagation of action potentials through networks of neuron-neuron and neuron-glia. Previous studies demonstrated that these associations are necessary for small GTPases activation in neurons. Especially, it is well known that small GTPases play a key role in neurite outgrowth, which is one of the most important events in neuronal development. Recent studies also have identified and characterized that molecular mechanisms of membrane trafficking and actin cytoskeleton formation/reorganization in migrating cells mediated by ADP-ribosylation factor 6 (Arf6) and its regulator cytohesin-2 are required for cell migration and neurite outgrowth. However, it have not completely established yet whether Arf6 activation is necessary or not in molecular mechanisms of neurite outgrowth. Our recent studies first identified and characterized that the previous unknown functional coiled-coil containing protein 120 (CCDC120) binds to cytohesin-2 and coordinately regulates neurite outgrowth in neuronal cells. This review summarizes the process that has been made in our understanding about the necessity of Arf6 activation in neurite outgrowth and the signaling transduction including cytohesin-2-CCDC120 complex in neuronal cells.