A novel role of brain-type ACS4 isotype in neuronal differentiation

Acyl-CoA synthetase (ACS4) is an arachidonate preferring acyl-CoA synthetase and has been shown to play an important role in lipid metabolism. Although arachidonate and decosahexanoate play a key role in lipid metabolism and in the brain, the mechanisms of its action are still not clearly understood. In this study, we identified brain-type ACS4 mRNA by 5'-RACE. We also confirmed that the mRNA in TT2 ES cells encoded a novel ACS4 protein, which contains 41 amino acids at its N-terminus. Furthermore, we found that ACS4 proteins were up-regulated in PC-12 cell by stimulation with nerve growth factor (NGF). Importantly, knockout of ACS4 in ES cells markedly attenuated neuronal differentiation induced by NGF and all-trans retinoic acids (RA). These results indicate that the ACS4 protein specifically expressed in brain plays an important role in arachidonate metabolism and neuronal differentiation in the brain.