Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain
Open accessAbstract
Diacylglycerol (DAG) lipase activity is required for axonal growth during development and for retrograde synaptic signaling at mature synapses. This enzyme synthesizes the endocannabinoid 2-arachidonoyl-glycerol (2-AG), and the CB1 cannabinoid receptor is also required for the above responses. We now report on the cloning and enzymatic characterization of the first specific sn-1 DAG lipases. Two closely related genes have been identified and their expression in cells correlated with 2-AG biosynthesis and release. The expression of both enzymes changes from axonal tracts in the embryo to dendritic fields in the adult, and this correlates with the developmental change in requirement for 2-AG synthesis from the pre- to the postsynaptic compartment. This switch provides a possible explanation for a fundamental change in endocannabinoid function during brain development. Identification of these enzymes may offer new therapeutic opportunities for a wide range of disorders.
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DAGL α and β transform diacylglycerols into 2-AG.
“In contrast, diacylglycerol lipase (DAGL) α and β transform diacylglycerols into 2-AG (Bisogno et al, 2003;Gao et al, 2010;Tanimura et al, 2010).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Bisogno et al, 2003
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- Authors
- Bisogno, T., Howell, F., Williams, G., Minassi, A., Cascio, M. G., Ligresti, A., Matias, I., Schiano-Moriello, A., Paul, P., Williams, E.-J., Gangadharan, U., Hobbs, C., Di Marzo, V., & Doherty, P.
- Affiliations
- Istituto di Chimica Biomolecolare (IT)
- King's College London (GB)
- 1Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Comprensorio Olivetti, 80078 Pozzuoli, Italy
- Corresponding author
- Doherty, Patrick
- ORCID
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2003-11-10
- Volume
- 163
- Issue
- 3
- Pages
- 463-468
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2173631
- OpenAlex
- W2166806732
- Cited by
- 1,039
- References
- 21
- Citations by year
- 2026: 20 · 2025: 31 · 2024: 34 · 2023: 33 · 2022: 54 · 2021: 48 · 2020: 33 · 2019: 46 · 2018: 41 · 2017: 39 · 2016: 47 · 2015: 61 · 2014: 51 · 2013: 57 · 2012: 53
- FWCI
- 21.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- diacylglycerol lipase, 2-arachidonoylglycerol, endocannabinoid signaling, CB1 receptor, axon growth, brain development, gene cloning, enzyme characterization, dendrites, postsynaptic compartment
- MeSH terms
- Animals, Arachidonic Acids, Brain, Cell Differentiation, Cloning, Molecular, Dendrites, Enzyme Inhibitors, Glycerides, Growth Substances, Humans, Lipoprotein Lipase, Molecular Sequence Data, Sequence Homology, Nucleic Acid, Synaptic Membranes, Time Factors, Signal Transduction, Neurites, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Presynaptic Terminals, DNA, Complementary, COS Cells, Mice, Rats, Cannabinoid Receptor Modulators, Endocannabinoids
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