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.
Department of Pharmacology, Temple University, School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
Heather A
HA
Bilson
Deanah L
DL
Mitchell
Barrie
B
Ashby
D002460:Cell Line; D017931:DNA Primers; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007668:Kidney; D016297:Mutagenesis, Site-Directed; D020033:Protein Isoforms / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D014162:Transfection; D014599:Uterus
D017931:DNA Primers; C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; D020033:Protein Isoforms; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011994:Recombinant Proteins; D015232:Dinoprostone