Binda et al. describe how the localization and activity of the prostaglandin receptor DP1 is regulated by its association with the enzyme that synthesizes its ligand.
DP1 is a G protein–coupled receptor activated by the prostaglandin PGD2. Much of the receptor is retained inside of the cell instead of being exported to the plasma membrane. Binda et al. discovered that the enzyme that synthesizes PGD2, L-PGDS, binds to DP1 and colocalizes with the receptor in the endoplasmic reticulum and Golgi apparatus.
L-PGDS enhances DP1’s transport to the plasma membrane, the researchers found. Overexpressing the enzyme boosted DP1’s expression on the cell surface, whereas knocking down L-PGDS reduced the receptor’s export. L-PGDS promoted DP1 export by recruiting the chaperone Hsp90 into a complex containing both the receptor and the prostaglandin synthase. Abolishing the interaction between Hsp90 and L-PGDS, or inhibiting the chaperone with geldanamycin, prevented L-PGDS from stimulating DP1 export. The chaperone might help DP1 to fold correctly or regulate the vesicle transport machinery that delivers the receptor to the cell surface.
L-PGDS enhanced prostaglandin signaling by promoting DP1’s transport to the plasma membrane. But the receptor–enzyme interaction might also increase DP1 signaling inside the cell; DP1 stimulated L-PGDS’ enzymatic activity, generating PGD2 that could potentially activate the receptor intracellularly. Indeed, L-PGDS and DP1 formed a complex with activated ERK kinases—downstream effectors of DP1—in the perinuclear region of cells. Senior author Jean-Luc Parent now wants to distinguish the effects of intracellular and cell surface DP1 signaling pathways.
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Text By Ben Short
