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首个sn1-二酰甘油脂肪酶的克隆揭示了大脑中内源性大麻素信号传导的空间和时间调控。

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

作者信息

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

机构信息

Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Comprensorio Olivetti, 80078 Pozzuoli, Italy.

出版信息

J Cell Biol. 2003 Nov 10;163(3):463-8. doi: 10.1083/jcb.200305129.

DOI:10.1083/jcb.200305129
PMID:14610053
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2173631/
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.

摘要

在发育过程中轴突生长以及成熟突触处逆行突触信号传导都需要二酰基甘油（DAG）脂肪酶活性。该酶合成内源性大麻素2-花生四烯酸甘油酯（2-AG），上述反应也需要CB1大麻素受体。我们现在报告首个特异性sn-1 DAG脂肪酶的克隆及酶学特性。已鉴定出两个密切相关的基因，它们在细胞中的表达与2-AG的生物合成和释放相关。这两种酶的表达从胚胎期的轴突束转变为成年期的树突区域，这与从突触前到突触后区室对2-AG合成需求的发育变化相关。这种转变为大脑发育过程中内源性大麻素功能的根本变化提供了一种可能的解释。鉴定出这些酶可能为多种疾病提供新的治疗机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/b536dd1f277d/200305129f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/f7481cc444a8/200305129f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/7e76503cc13b/200305129f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/8f4fdf24d5c3/200305129f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/bd077d39421b/200305129f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/b536dd1f277d/200305129f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/f7481cc444a8/200305129f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/7e76503cc13b/200305129f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/8f4fdf24d5c3/200305129f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/bd077d39421b/200305129f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c426/2173631/b536dd1f277d/200305129f5.jpg

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