P4-ATPase ATP8A2 acts in synergy with CDC50A to enhance neurite outgrowth

P4-ATPases are lipid flippases that transport phospholipids across cellular membranes, playing vital roles in cell function. In humans, the disruption of the P4-ATPase ATP8A2 gene causes a severe neurological phenotype. Here, we found that Atp8a2 mRNA was highly expressed in PC12 cells, hippocampal neurons and the brain. Overexpression of ATP8A2 increased the length of neurite outgrowth in NGF-induced PC12 cells and in primary cultures of rat hippocampal neurons. Inducing the loss of function of CDC50A in hippocampal neurons via RNA interference reduced neurite outgrowth, and the co-overexpression of CDC50A and ATP8A2 in PC12 cells enhanced NGF-induced neurite outgrowth. These results indicate that ATP8A2, acting in synergy with CDC50A, performs an important role in neurite outgrowth in neurons.

► P4-ATPase Atp8a2 was expressed in PC12 cells, hippocampal neurons and the brain.
► ATP8A2 enhances neurite outgrowth in NGF-induced PC12 cells.
► ATP8A2 increases axon length in rat hippocampal neurons.
► CDC50A acts in synergy with ATP8A2 to enhance the neurite outgrowth.