QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 6, 2004, 24(40):8752-8761; doi:10.1523/JNEUROSCI.3155-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Bhattacharya, M. Articles by Ferguson, S. S. G. Search for Related Content PubMed PubMed Citation Articles by Bhattacharya, M. Articles by Ferguson, S. S. G.

 Previous Article  |  Next Article 

Cellular/Molecular
Ral and Phospholipase D2-Dependent Pathway for Constitutive Metabotropic Glutamate Receptor Endocytosis

Moshmi Bhattacharya,^1 * Andy V. Babwah,^1 * Christina Godin,¹ Pieter H. Anborgh,¹ Lianne B. Dale,¹ Michael O. Poulter,³ and Stephen S. G. Ferguson^1,2

¹Cell Biology Research Group, Robarts Research Institute, London, Ontario, Canada N6A 5K8, ²Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A 5C1, and ³Neuroscience Research Institute, Carleton University, Ottawa, Ontario, Canada K1S 5B6

G-protein-coupled receptors play a central role in the regulation of neuronal cell communication. Class 1 metabotropic glutamate receptors (mGluRs) mGluR1a and mGluR5a, which are coupled with the hydrolysis of phosphoinositides, are essential for modulating excitatory neurotransmission at glutamatergic synapses. These receptors are constitutively internalized in heterologous cell cultures, neuronal cultures, and intact neuronal tissues. We show here that the small GTP-binding protein Ral, its guanine nucleotide exchange factor RalGDS (Ral GDP dissociation stimulator), and phospholipase D2 (PLD2) are constitutively associated with class 1 mGluRs and regulate constitutive mGluR endocytosis. Moreover, both Ral and PLD2 are colocalized with mGluRs in endocytic vesicles in both human embryonic kidney 293 (HEK 293) cells and neurons. Ral and PLD2 activity is required for the internalization of class 1 mGluRs but is not required for the internalization of the ₂-adrenergic receptor. Constitutive class 1 mGluR internalization is not dependent on the downstream Ral effector proteins Ral-binding protein 1 and PLD1 or either ADP-ribosylation factors ARF1 or ARF6. The treatment of HEK 293 cells and neurons with small interfering RNA both downregulates PLD2 expression and blocks mGluR1a and mGluR5a endocytosis. The constitutive internalization of mGluR1a and mGluR5a is also attenuated by the treatment of cells with 1-butanol to prevent PLD2-mediated phosphatidic acid formation. We propose that the formation of a mGluR-scaffolded RalGDS/Ral/PLD2 protein complex provides a novel alternative mechanism to -arrestins for the constitutive endocytosis of class 1 mGluRs.

Key words: G-protein-coupled receptor; Ral GTP-binding protein; phospholipase D; endocytosis; metabotropic glutamate receptor; glutamate

---

Received April 8, 2004; revised August 18, 2004; accepted August 19, 2004.

This article has been cited by other articles:

				J. A. Grodnitzky, N. Syed, M. J. Kimber, T. A. Day, J. G. Donaldson, and W. H. Hsu Somatostatin Receptors Signal through EFA6A-ARF6 to Activate Phospholipase D in Clonal beta-Cells J. Biol. Chem., May 4, 2007; 282(18): 13410 - 13418. [Abstract] [Full Text] [PDF]

				M. Behrens, J. Bartelt, C. Reichling, M. Winnig, C. Kuhn, and W. Meyerhof Members of RTP and REEP Gene Families Influence Functional Bitter Taste Receptor Expression J. Biol. Chem., July 21, 2006; 281(29): 20650 - 20659. [Abstract] [Full Text] [PDF]

				D. Padron, R. D. Tall, and M. G. Roth Phospholipase D2 Is Required for Efficient Endocytic Recycling of Transferrin Receptors Mol. Biol. Cell, February 1, 2006; 17(2): 598 - 606. [Abstract] [Full Text] [PDF]

				G. Lalli and A. Hall Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex J. Cell Biol., December 5, 2005; 171(5): 857 - 869. [Abstract] [Full Text] [PDF]

				J. C. Cuellar, E. L. Griffith, and L. R. Merlin Contrasting Roles of Protein Kinase C in Induction Versus Suppression of Group I mGluR-Mediated Epileptogenesis In Vitro J Neurophysiol, November 1, 2005; 94(5): 3643 - 3647. [Abstract] [Full Text] [PDF]

				P. H. Anborgh, C. Godin, M. Pampillo, G. K. Dhami, L. B. Dale, S. P. Cregan, R. Truant, and S. S. G. Ferguson Inhibition of Metabotropic Glutamate Receptor Signaling by the Huntingtin-binding Protein Optineurin J. Biol. Chem., October 14, 2005; 280(41): 34840 - 34848. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help