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

Tiziana Bisogno; Fiona Howell; Gaseth Williams; Alberto Minassi; Maria Grazia Cascio; Alessia Ligresti; Isabel Matias; Aniello Schiano-Moriello; Praveen Paul; Emma Jane Williams; Uma Gangadbaran; Carl Hobbs; Vincenzo Di Marzo; Patrick Doherty

doi:10.1083/jcb.200305129

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

Tiziana Bisogno, Fiona Howell, Gaseth Williams, Alberto Minassi, Maria Grazia Cascio, Alessia Ligresti, Isabel Matias, Aniello Schiano-Moriello, Praveen Paul, Emma Jane Williams, Uma Gangadbaran, Carl Hobbs, Vincenzo Di Marzo, Patrick Doherty^*

^*Corresponding author for this work

Medical Sciences

Research output: Contribution to journal › Article › peer-review

871 Citations (Scopus)

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.

Original language	English
Pages (from-to)	463-468
Number of pages	6
Journal	Journal of Cell Biology
Volume	163
Issue number	3
DOIs	https://doi.org/10.1083/jcb.200305129
Publication status	Published - 10 Nov 2003

Bibliographical note

Acknowledgement:
TaqMan analysis was performed by K. Philpott and R. Davies (GlaxoSmithKline, Harlow, UK).

This work was supported by the Wellcome Trust, Volkswagen Stiftung, Italian Ministry of Education, University and Research (Fondo per gli Investimenti della Ricerca di Base), and the UK Medical Research Council. A Human Frontier in Science Program Organization fellowship partly supported T. Bisogno.

Keywords

Anandamide
Axonal growth
CB1 receptor
Diacylglycerol lipase
Synaptic plasticity

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Bisogno, T., Howell, F., Williams, G., Minassi, A., Cascio, M. G., Ligresti, A., Matias, I., Schiano-Moriello, A., Paul, P., Williams, E. J., Gangadbaran, U., Hobbs, C., Di Marzo, V., & Doherty, P. (2003). Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. Journal of Cell Biology, 163(3), 463-468. https://doi.org/10.1083/jcb.200305129

Bisogno, T, Howell, F, Williams, G, Minassi, A, Cascio, MG, Ligresti, A, Matias, I, Schiano-Moriello, A, Paul, P, Williams, EJ, Gangadbaran, U, Hobbs, C, Di Marzo, V & Doherty, P 2003, 'Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain', Journal of Cell Biology, vol. 163, no. 3, pp. 463-468. https://doi.org/10.1083/jcb.200305129

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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.",

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author = "Tiziana Bisogno and Fiona Howell and Gaseth Williams and Alberto Minassi and Cascio, {Maria Grazia} and Alessia Ligresti and Isabel Matias and Aniello Schiano-Moriello and Praveen Paul and Williams, {Emma Jane} and Uma Gangadbaran and Carl Hobbs and {Di Marzo}, Vincenzo and Patrick Doherty",

note = "Acknowledgement: TaqMan analysis was performed by K. Philpott and R. Davies (GlaxoSmithKline, Harlow, UK). This work was supported by the Wellcome Trust, Volkswagen Stiftung, Italian Ministry of Education, University and Research (Fondo per gli Investimenti della Ricerca di Base), and the UK Medical Research Council. A Human Frontier in Science Program Organization fellowship partly supported T. Bisogno. ",

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AU - Minassi, Alberto

AU - Cascio, Maria Grazia

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AU - Schiano-Moriello, Aniello

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AU - Gangadbaran, Uma

AU - Hobbs, Carl

AU - Di Marzo, Vincenzo

AU - Doherty, Patrick

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

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