title: Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain.
abstract: 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.
authors: Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Comprensorio Olivetti, 80078 Pozzuoli, Italy.
authors: Tiziana
authors: T
authors: Bisogno
authors: Fiona
authors: F
authors: Howell
authors: Gareth
authors: G
authors: Williams
authors: Alberto
authors: A
authors: Minassi
authors: Maria Grazia
authors: MG
authors: Cascio
authors: Alessia
authors: A
authors: Ligresti
authors: Isabel
authors: I
authors: Matias
authors: Aniello
authors: A
authors: Schiano-Moriello
authors: Praveen
authors: P
authors: Paul
authors: Emma-Jane
authors: EJ
authors: Williams
authors: Uma
authors: U
authors: Gangadharan
authors: Carl
authors: C
authors: Hobbs
authors: Vincenzo
authors: V
authors: Di Marzo
authors: Patrick
authors: P
authors: Doherty
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis*; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D019556:COS Cells; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D003712:Dendrites / Q000201:enzymology; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005989:Glycerides / Q000096:biosynthesis*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000302:isolation & purification*; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000187:drug effects / Q000201:enzymology; D017729:Presynaptic Terminals / Q000201:enzymology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D013570:Synaptic Membranes / Q000201:enzymology; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D018076:DNA, Complementary; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D006133:Growth Substances; C094503:glyceryl 2-arachidonate; C480280:DAGLA protein, human; C480281:DAGLB protein, human; D008071:Lipoprotein Lipase