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First published online 26 March 2003
doi: 10.1242/jcs.00397

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Agonist-induced endocytosis of lysophosphatidic acid-coupled LPA₁/EDG-2 receptors via a dynamin2- and Rab5-dependent pathway

Mandi M. Murph^1,*, Launa A. Scaccia^1,*, Laura A. Volpicelli² and Harish Radhakrishna^1,

¹ School of Biology and Petit Institute for Biosciences and Bioengineering, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA
² Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA

Author for correspondence (e-mail: harish.radhakrishna{at}biology.gatech.edu)

Accepted 28 January 2003

Lysophosphatidic acid (LPA) is a serum-borne phospholipid that exerts a pleiotropic range of effects on cells through activation of three closely related G-protein-coupled receptors termed LPA₁/EDG-2, LPA₂/EDG-4 and LPA₃/EDG-7. Of these receptors, the LPA₁ receptor is the most widely expressed. In this study, we investigated the agonist-induced endocytosis of the human LPA₁ receptor, bearing an N-terminal FLAG epitope tag, in stably transfected HeLa cells. Treatment with LPA induced the rapid endocytosis of approximately 40% of surface LPA₁ within 15 minutes. Internalization was both dose dependent and LPA specific since neither lysophophatidylcholine nor sphingosine-1-phosphate induced LPA₁ endocytosis. Removal of agonist following 30 minutes incubation resulted in recycling of LPA₁ back to the cell surface. LPA₁ internalization was strongly inhibited by dominant-inhibitory mutants of both dynamin2 (K44A) and Rab5a (S34N). In addition, both dynamin2 K44A and Rab5 S34N mildly inhibited LPA₁-dependent activation of serum response factor. Finally, our results also indicate that LPA₁ exhibits basal, LPA-dependent internalization in the presence of serum-containing medium.

Key words: LPA₁, Endocytosis, Dynamin, Rab5, Lysophosphatidic acid

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