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

Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of... 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. diacylglycerol lipase; CB1 receptor; anandamide; axonal growth; synaptic plasticity Footnotes T. Bisogno, F. Howell, and G. Williams contributed equally to this work. Abbreviations used in this paper: 2-AG, 2-arachidonoyl-glycerol; BDNF, brain-derived neuronotrophic factor; DAGL, DAG lipase; THL, tetrahydrolipstatin. Submitted: 28 May 2003 Accepted: 24 September 2003 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

Loading next page...
 
/lp/rockefeller-university-press/cloning-of-the-first-sn1-dag-lipases-points-to-the-spatial-and-HcBINWFTD0
Publisher
Rockefeller University Press
Copyright
© 2003 Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.200305129
pmid
14610053
Publisher site
See Article on Publisher Site

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. diacylglycerol lipase; CB1 receptor; anandamide; axonal growth; synaptic plasticity Footnotes T. Bisogno, F. Howell, and G. Williams contributed equally to this work. Abbreviations used in this paper: 2-AG, 2-arachidonoyl-glycerol; BDNF, brain-derived neuronotrophic factor; DAGL, DAG lipase; THL, tetrahydrolipstatin. Submitted: 28 May 2003 Accepted: 24 September 2003

Journal

The Journal of Cell BiologyRockefeller University Press

Published: Nov 10, 2003

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off