Zhou, Y;
Howell, FV;
Glebov, OO;
Albrecht, D;
Williams, G;
Doherty, P;
(2016)
Regulated endosomal trafficking of Diacylglycerol lipase alpha (DAGLα) generates distinct cellular pools; implications for endocannabinoid signaling.
Molecular and Cellular Neuroscience
, 76
pp. 76-86.
10.1016/j.mcn.2016.08.011.
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Abstract
Diacylglycerol lipase alpha (DAGLα) generates the endocannabinoid (eCB) 2-arachidonylglycerol (2-AG) that regulates the proliferation and differentiation of neural stem cells and serves as a retrograde signaling lipid at synapses. Nothing is known about the dynamics of DAGLα expression in cells and this is important as it will govern where 2-AG can be made and released. We have developed a new construct to label DAGLα at the surface of live cells and follow its trafficking. In hippocampal neurons a cell surface pool of DAGLα co-localizes with Homer, a postsynaptic density marker. This surface pool of DAGLα is dynamic, undergoing endocytosis and recycling back to the postsynaptic membrane. A similar cycling is seen in COS-7 cells with the internalized DAGLα initially transported to EEA1 and Rab5-positive early endosomes via a clathrin-independent pathway before being transported back to the cell surface. The internalized DAGLα is present on reticular structures that co-localize with microtubules. Importantly, DAGLα cycling is a regulated process as inhibiting PKC results in a significant reduction in endocytosis. This is the first description of DAGLα cycling between the cell surface and an intracellular endosomal compartment in a manner that can regulate the level of the enzyme at the cell surface.
Type: | Article |
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Title: | Regulated endosomal trafficking of Diacylglycerol lipase alpha (DAGLα) generates distinct cellular pools; implications for endocannabinoid signaling |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.mcn.2016.08.011 |
Publisher version: | http://dx.doi.org/10.1016/j.mcn.2016.08.011 |
Language: | English |
Additional information: | Copyright © 2016. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0. Access may be initially restricted by the publisher. |
Keywords: | DAGLα; Endosomes; Endocytosis; Trafficking; Endocannabinoid; 2-AG |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
URI: | https://discovery.ucl.ac.uk/id/eprint/1537550 |
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