Human prostaglandin EP3 receptor isoforms show different agonist-induced internalization patterns.

The human prostaglandin EP3 receptor comprises eight isoforms that differ in carboxyl-tail. We show here that the isoforms are trafficked differently. When expressed in HEK293 cells, the isoforms located to the cell surface, although a fraction of some remained in the cell. Upon prostaglandin E(2) stimulation, EP3.I internalized almost completely, EP3.II, EP3.V, EP3.VI and EP3.f internalized to a lesser extent and EP3.III and EP3.IV did not internalize. Both EP3.I and EP3.f internalized with beta-arrestin and internalization were blocked by a dominant negative form of Eps15, a clathrin-associated protein. Although EP3.II internalized, beta-arrestin did not translocate with the receptor and internalization was not blocked by mutant Eps15. EP3.V and EP3.VI internalized to discrete areas of the cell with beta-arrestin.