Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain

By T. Bisogno, Fiona V. Howell, Gareth Williams, Alberto Minassi, M. Cascio, A. Ligresti, I. Matias, Aniello Schiano-Moriello, Praveen G. Paul, E. Williams and 4 more. Journal of Cell Biology, 2003

1,047 citations recorded by the source corpus.

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.

Subfields: Endocrinology, Diabetes and Metabolism, Pharmacology, Surgery

View Paper: https://www.semanticscholar.org/paper/403e445577c335cf973a9e9ef5d611718d9b2b7b

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In Pharmacology

1. V. Di Marzo
2. K. Mackie
3. George Kunos
4. P. Pacher
5. S. Batkai
6. Tamás F. Freund
7. Hui-Chen Lu
8. I. Katona

In Surgery

1. Tamás F. Freund
2. I. Katona
3. P. Pacher
4. S. Batkai
5. George Kunos
6. V. Di Marzo

Citations in the corpus

• An introduction to the endogenous cannabinoid system (2015, background): “Abbreviations: AA, arachidonic acid; ABHD4, alpha/beta domaincontaining hydrolase 4; ABHD6, alpha/beta domain-containing hydrolase 6; ABHD12, alpha/beta domain-containing hydrolase 12; COX-2, cyclooxygenase-2; DAG, diacylglycerol; DAGL, diacylglycerol lipase; FAAH, fatty acid aminohydrolase; GDE-1, ”
• Endocannabinoid signaling as a synaptic circuit breaker in neurological disease (2008, background): “Moreover, CB 1 receptors share an evolutionary history with a recently identified major biosynthetic enzyme of 2-AG called diacylglycerol lipase-α (DGL-α”
• The Endocannabinoid System as an Emerging Target of Pharmacotherapy (2006, background): “Two DAG lipase isozymes, α and β, have been cloned (Bisogno et al., 2003).”
• Distribution of cannabinoid receptors in the central and peripheral nervous system. (2005, background): “The paper reporting the cloning of this enzyme did not perform a systematic analysis of its anatomical distribution (Bisogno et al. 2003).”
• Endocannabinoid signaling in the brain: biosynthetic mechanisms in the limelight (2010, background): “1b ), they are mostly produced by phospholipase Cβ (PLCβ) acting on membrane phosphatidylinositols, and then converted to 2-AG by the action of either of two isoforms of the same enzyme, the sn -1-diacylglycerol lipases α and β (DAGLα and DAGLβ”
• Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019, neutral): “Diacylglycerol Lipase Beta (Daglb) is involved in endocannabanoid production and affects axonal growth during development (Bisogno et al., 2003; Powell et al., 2015) (Figure S4D).”
• Effects of cannabinoids and cannabinoid‐enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes (2011, methodology): “…inhibitory effect of compounds on DAGLa was tested in COS cells overexpressing human DAGLa, the most abundant of the two DAGLs in the adult brain (Bisogno et al., 2003); wild-type (i.e. non-transfected) COS cells also exhibited DAGL activity but British Journal of Pharmacology (2011) 163…”
• Neurobiological Interactions Between Stress and the Endocannabinoid System (2016, background): “The synthesis of 2-AG is tightly coupled to the generation of diacylglycerol from phospholipase C activity, which is rapidly converted to 2-AG by the enzyme diacylglycerol lipase (Bisogno et al, 2003; Sugiura et al, 1995; Figure 1).”
• Distinct coincidence detectors govern the corticostriatal spike timing‐dependent plasticity (2010, background): “2-AG is a product of conversion of 1,2-DAG by diacylglycerol lipase α (DGLα) (Stella et al. 1997; Bisogno et al. 2003; Hashimotodani et al. 2005, 2008).”
• Endocannabinoid control of food intake and energy balance (2005, background): “Phospholipid-dependent pathways for endocannabinoid biosynthesis were discovered, leading to the cloning of the enzymes that catalyze the formation of anandamide and 2-AG from their direct precursors: the N -acylphosphatidylethanolamine-selective phospholipase D and the sn -1–selective diacylglyce”