Journal
JOURNAL OF CELL SCIENCE
Volume 116, Issue 10, Pages 1969-1980Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.00397
Keywords
LPA(1); endocytosis; dynamin; Rab5; lysophosphatidic acid
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Funding
- NHLBI NIH HHS [HL 67134] Funding Source: Medline
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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 LPA(1)/EDG-2, LPA(2)/EDG-4 and LPA(3)/EDG-7. Of these receptors, the LPA(1) receptor is the most widely expressed. In this study, we investigated the agonist-induced endocytosis of the human LPA(1) 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 LPA(1) within 15 minutes. Internalization was both dose dependent and LPA specific since neither lysophophatidylcholine nor sphingosine-1-phosphate induced LPA(1) endocytosis. Removal of agonist following 30 minutes incubation resulted in recycling of LPA(1) back to the cell surface. LPA(1) 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 LPA(1)-dependent activation of serum response factor. Finally, our results also indicate that LPA(1) exhibits basal, LPA-dependent internalization in the presence of serum-containing medium.
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