title: Endosomal trafficking of the G protein-coupled receptor somatostatin receptor 3.
abstract: Intracellular trafficking of G protein-coupled receptors (GPCRs) regulates their surface availability and determines cellular response to agonists. Rab GTPases regulate membrane trafficking and identifying Rab networks controlling GPCR trafficking is essential for understanding GPCR signaling. We used real time imaging to show that somatostatin receptor 3 (SSTR3) traffics through Rab4-, Rab21-, and Rab11-containing endosomes, but largely bypasses Rab5 and Rab7 endosomes. We show that SSTR3 rapidly traffics through Rab4 endosomes but moves slower through Rab21 and Rab11 endosomes. SSTR3 passage through each endosomal compartment is regulated by the cognate Rab since expression of the inactive Rab4/S22N, Rab21/T33N, and Rab11/S25N inhibits SSTR3 trafficking. Thus, Rab4, Rab21, and Rab11 may represent therapeutic targets to modulate surface availability of SSTR3 for agonist binding. Our novel finding that Rab21 regulates SSTR3 trafficking suggests that Rab21 may play a role in trafficking of other GPCRs.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, 1918 University Boulevard, McCallum 668, Birmingham, AL 35294, USA.
authors.forename: Cristy
authors.initials: C
authors.lastname: Tower-Gilchrist
authors.forename: Eunjoo
authors.initials: E
authors.lastname: Lee
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sztul
mesh_terms: D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D017481:Receptors, Somatostatin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020695:rab4 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D017481:Receptors, Somatostatin; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C103631:somatostatin receptor 3; C546392:rab21 protein, mouse