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Membranes 2014, 4(3), 302-318; doi:10.3390/membranes4030302

Role of Phospholipase D in G-Protein Coupled Receptor Function

1,* , 1
1 Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, D-52074 Aachen, Germany 2 Department of Pharmacology and Toxicology, Otto-von-Guericke-University Magdeburg, D-39120 Magdeburg, Germany
* Author to whom correspondence should be addressed.
Received: 29 May 2014 / Revised: 24 June 2014 / Accepted: 25 June 2014 / Published: 3 July 2014
(This article belongs to the Special Issue Trafficking of Membrane Receptors)
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Prolonged agonist exposure of many G-protein coupled receptors induces a rapid receptor phosphorylation and uncoupling from G-proteins. Resensitization of these desensitized receptors requires endocytosis and subsequent dephosphorylation. Numerous studies show the involvement of phospholipid-specific phosphodiesterase phospholipase D (PLD) in the receptor endocytosis and recycling of many G-protein coupled receptors e.g., opioid, formyl or dopamine receptors. The PLD hydrolyzes the headgroup of a phospholipid, generally phosphatidylcholine (PC), to phosphatidic acid (PA) and choline and is assumed to play an important function in cell regulation and receptor trafficking. Protein kinases and GTP binding proteins of the ADP-ribosylation and Rho families regulate the two mammalian PLD isoforms 1 and 2. Mammalian and yeast PLD are also potently stimulated by phosphatidylinositol 4,5-bisphosphate. The PA product is an intracellular lipid messenger. PLD and PA activities are implicated in a wide range of physiological processes and diseases including inflammation, diabetes, oncogenesis or neurodegeneration. This review discusses the characterization, structure, and regulation of PLD in the context of membrane located G-protein coupled receptor function.
Keywords: phospholipase D; G-protein coupled receptor; internalization; endocytosis; desensitization; recycling; resensitization phospholipase D; G-protein coupled receptor; internalization; endocytosis; desensitization; recycling; resensitization
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Brandenburg, L.-O.; Pufe, T.; Koch, T. Role of Phospholipase D in G-Protein Coupled Receptor Function. Membranes 2014, 4, 302-318.

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