| First Author | van Esbroeck ACM | Year | 2019 |
| Journal | Front Mol Neurosci | Volume | 12 |
| Pages | 286 | PubMed ID | 31849602 |
| Mgi Jnum | J:335248 | Mgi Id | MGI:6782492 |
| Doi | 10.3389/fnmol.2019.00286 | Citation | van Esbroeck ACM, et al. (2019) Identification of alpha,beta-Hydrolase Domain Containing Protein 6 as a Diacylglycerol Lipase in Neuro-2a Cells. Front Mol Neurosci 12:286 |
| abstractText | The endocannabinoid 2-arachidonoylglycerol (2-AG) is involved in neuronal differentiation. This study aimed to identify the biosynthetic enzymes responsible for 2-AG production during retinoic acid (RA)-induced neurite outgrowth of Neuro-2a cells. First, we confirmed that RA stimulation of Neuro-2a cells increases 2-AG production and neurite outgrowth. The diacylglycerol lipase (DAGL) inhibitor DH376 blocked 2-AG production and reduced neuronal differentiation. Surprisingly, CRISPR/Cas9-mediated knockdown of DAGLalpha and DAGLbeta in Neuro-2a cells did not reduce 2-AG levels, suggesting another enzyme capable of producing 2-AG in this cell line. Chemical proteomics revealed DAGLbeta and alpha,beta-hydrolase domain containing protein (ABHD6) as the only targets of DH376 in Neuro-2a cells. Biochemical, genetic and lipidomic studies demonstrated that ABHD6 possesses DAGL activity in conjunction with its previously reported monoacylglycerol lipase activity. RA treatment of Neuro-2a cells increased by three-fold the amount of active ABHD6. Our study shows that ABHD6 exhibits significant DAG lipase activity in Neuro-2a cells in addition to its known MAG lipase activity and suggest it is involved in neuronal differentiation. |
