| Title : Identification of alpha,beta-Hydrolase Domain Containing Protein 6 as a Diacylglycerol Lipase in Neuro-2a Cells - van Esbroeck_2019_Front.Mol.Neurosci_12_286 |
| Author(s) : van Esbroeck ACM , Kantae V , Di X , van der Wel T , den Dulk H , Stevens AF , Singh S , Bakker AT , Florea BI , Stella N , Overkleeft HS , Hankemeier T , van der Stelt M |
| Ref : Front Mol Neurosci , 12 :286 , 2019 |
| Abstract : 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. |
| ESTHER : van Esbroeck_2019_Front.Mol.Neurosci_12_286 |
| PubMedSearch : van Esbroeck_2019_Front.Mol.Neurosci_12_286 |
| PubMedID: 31849602 |
| Gene_locus related to this paper: human-ABHD6 |
| Gene_locus related to this paper: human-ABHD6 |
van Esbroeck ACM, Kantae V, Di X, van der Wel T, den Dulk H, Stevens AF, Singh S, Bakker AT, Florea BI, Stella N, Overkleeft HS, Hankemeier T, van der Stelt M (2019)
Identification of alpha,beta-Hydrolase Domain Containing Protein 6 as a Diacylglycerol Lipase in Neuro-2a Cells
Front Mol Neurosci
12 :286
van Esbroeck ACM, Kantae V, Di X, van der Wel T, den Dulk H, Stevens AF, Singh S, Bakker AT, Florea BI, Stella N, Overkleeft HS, Hankemeier T, van der Stelt M (2019)
Front Mol Neurosci
12 :286