Medium chain fatty acid acyl‐CoA synthetase ACSF2 may play a role in neuronal differentiation

Acyl-CoA synthetases (ACS) activate fatty acids by forming a thioester bond with CoA. We identified ACSF2 (ACS family, member 2; previously referred to as ACSMw) as an ACS that did not fit clearly into sub-families of enzymes that activate short-, medium-, long-, and very long-chain fatty acid substrates. We previously reported that ACSF2 is ubiquitously expressed, and is abundant in brain. We also reported that although structurally ACSF2 does not belong to the medium-chain ACS subfamily, its preferred substrates are saturated fatty acids containing 6-10 carbons. Kinetic studies of overexpressed ACSF2 revealed a Km app of 24 uM and a broad optimal pH range of 7-8.5 when assayed with C8:0. RNA interference studies in mouse neuroblastoma Neuro2a cells revealed that ACSF2 is the major medium-chain ACS in this cell line. In undifferentiated Neuro2a cells, ACSF2 colocalized with Golgi markers. However, after differentiation in culture with retinoic acid, the protein migrated to nodes, branch points, and termini of developing neurites. Partial colocalization of ACSF2 with the synaptic vesicle protein, synaptophysin, was observed in differentiated cells. In contrast, differentiation of Neuro2a cells with dibutytyl cAMP induced translocation of ACSF2 to the nucleus. Further studies to elucidate the role of ACSF2 in neuronal differentiation are in progress. Supported by NIH grants NS37355 and HD10981.