Department of Cell Biology, University of Alabama at Birmingham, 1918 University Boulevard, McCallum 668, Birmingham, AL 35294, USA.
Biochem Biophys Res Commun. 2011 Oct 7;413(4):555-60. doi: 10.1016/j.bbrc.2011.08.137. Epub 2011 Sep 7.
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.
G 蛋白偶联受体 (GPCRs) 的细胞内转运调节其表面可用性，并决定细胞对激动剂的反应。Rab GTPases 调节膜转运，识别控制 GPCR 转运的 Rab 网络对于理解 GPCR 信号转导至关重要。我们使用实时成像技术显示，生长抑素受体 3 (SSTR3) 通过含有 Rab4、Rab21 和 Rab11 的内体运输，但主要绕过 Rab5 和 Rab7 内体。我们表明，SSTR3 可快速通过 Rab4 内体运输，但通过 Rab21 和 Rab11 内体运输速度较慢。每个内体隔室中 SSTR3 的通过都受到相应 Rab 的调节，因为表达无活性的 Rab4/S22N、Rab21/T33N 和 Rab11/S25N 会抑制 SSTR3 的运输。因此，Rab4、Rab21 和 Rab11 可能代表治疗靶点，以调节 SSTR3 与激动剂结合的表面可用性。我们的新发现表明，Rab21 调节 SSTR3 的运输，这表明 Rab21 可能在其他 GPCR 的运输中发挥作用。
