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

Journal of Cell Biology - Tập 163 Số 3 - Trang 463-468 - 2003
Tiziana Bisogno1, Fiona V. Howell2, Gareth Williams2, Alberto Minassi1, Maria Grazia Cascio1, Alessia Ligresti1, Isabel Matias1, Aniello Schiano Moriello1, Praveen Paul2, Emma-Jane Williams2, Uma Gangadharan2, Carl Hobbs2, Vincenzo Di Marzo1, Patrick Doherty2
11Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Comprensorio Olivetti, 80078 Pozzuoli, Italy
22Molecular Neurobiology Group, Medical Research Council Centre for Developmental Neurobiology, King's College London, London Bridge, London SE1 1UL, UK

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

1997, Biochem. J., 322, 671, 10.1042/bj3220671

2002, Brain Res. Mol. Brain Res., 106, 101, 10.1016/S0169-328X(02)00417-5

1996, Mol. Cell. Neurosci., 8, 120, 10.1006/mcne.1996.0051

2002, J. Neurosci., 22, 200, 10.1523/JNEUROSCI.22-01-00200.2002

1998, Trends Neurosci., 21, 521, 10.1016/S0166-2236(98)01283-1

2000, FASEB J., 14, 1432, 10.1096/fasebj.14.10.1432

2001, Nature., 410, 822, 10.1038/35071088

1997, Pancreas., 14, 301, 10.1097/00006676-199704000-00014

1998, FEBS Lett., 429, 152, 10.1016/S0014-5793(98)00581-X

2001, Neuron., 29, 717, 10.1016/S0896-6273(01)00246-X

1995, Biochim. Biophys. Acta., 1254, 311, 10.1016/0005-2760(94)00193-3

2002, Nature., 418, 530, 10.1038/nature00839

1995, Biochem. Pharmacol., 50, 83

2001, Nature., 413, 527, 10.1038/35097089

1997, Pharmacol. Ther., 74, 129

1997, Nature., 388, 773, 10.1038/42015

1995, Biochem. Biophys. Res. Commun., 215, 89, 10.1006/bbrc.1995.2437

2003, J. Cell Biol., 160, 481, 10.1083/jcb.200210164

2002, Science., 296, 678, 10.1126/science.1063545

1991, Gene., 103, 61, 10.1016/0378-1119(91)90391-N

Thông tin
Thông tin xuất bản

Journal of Cell Biology

Tập 163 Số 3

463-468

Thông tin tác giả