Lysophosphatidic acid receptor LPA 1 trafficking and interaction with Rab proteins, as evidenced by Förster resonance energy transfer.

LPA ₁ internalization to endosomes was studied employing Förster Resonance Energy Transfer (FRET) in cells coexpressing the mCherry-lysophosphatidic acid LPA ₁ receptors and distinct eGFP-tagged Rab proteins. Lysophosphatidic acid (LPA)-induced internalization was rapid and decreased afterward: phorbol myristate acetate (PMA) action was slower and sustained. LPA stimulated LPA ₁ -Rab5 interaction rapidly but transiently, whereas PMA action was rapid but sustained. Expression of a Rab5 dominant-negative mutant blocked LPA ₁ -Rab5 interaction and receptor internalization. LPA-induced LPA ₁ -Rab9 interaction was only observed at 60 min, and LPA ₁ -Rab7 interaction after 5 min with LPA and after 60 min with PMA. LPA triggered immediate but transient rapid recycling (i.e., LPA ₁ -Rab4 interaction), whereas PMA action was slower but sustained. Agonist-induced slow recycling (LPA ₁ -Rab11 interaction) increased at 15 min and remained at this level, whereas PMA action showed early and late peaks. Our results indicate that LPA ₁ receptor internalization varies with the stimuli.
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