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First published online 5 June 2007
doi: 10.1242/jcs.005611

Journal of Cell Science 120, 2171-2178 (2007)
Published by The Company of Biologists 2007
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Research Article

Role of a G{alpha}i2 protein splice variant in the formation of an intracellular dopamine D2 receptor pool

Manuel F. López-Aranda1,*, Maria J. Acevedo1,*, Antonia Gutierrez2, Peter Koulen3 and Zafar U. Khan1,{ddagger}

1 Neurobiology Laboratory, CIMES, Faculty of Medicine, University of Malaga, Campus Teatinos s/n, 29071-Malaga, Spain
2 Department of Cell Biology, Faculty of Science, University of Malaga, Campus Teatinos s/n, 29071-Malaga, Spain
3 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA

{ddagger} Author for correspondence (e-mail: zkhan{at}uma.es)

Accepted 1 May 2007

Treatment of D2-receptor-expressing cells with specific drugs upregulates the receptor number at the cell surface independently of protein synthesis, leading to the concept of an intracellular receptor pool. However, how this pool is operating is still an enigma. Here, we report that a splice variant of the G{alpha}i2 protein, protein sG{alpha}i2, plays a crucial role in the maintenance of this D2-receptor pool. Co-expression of sGi2 with D2 receptor reduced receptor localization to cell surface by one-third. This effect is associated with specific intracellular protein-protein interaction and the formation of a sGi2–D2-receptor complex. It has been suggested that the formation of this complex serves to prevent D2 receptors from reaching the cell membrane. Treatment of D2-receptor-expressing cells with agonists increased the number of cell surface D2 receptors and coincided with a reduction in these receptors from intracellular complexes, suggesting that agonist treatment released D2 receptors from the complex allowing them to localize to the cell membrane. Thus, in addition to elucidating how the intracellular pool of D2 receptor functions, our findings uncover a novel mechanism regulating the density of cell surface D2 receptors.

Key words: Protein-protein interaction, Intracellular receptor pool, D2 receptor, G{alpha}i2 protein, Receptor upregulation, Receptor density


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© The Company of Biologists Ltd 2007