The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

• DOI: 10.1016/j.celrep.2017.10.011
• Publication Date: 2017-10-26T10:19:59Z
• Authors: Chunman Li; Zhe Wei; Yi Fan; Wei Huang; Yunchao Su; Honglin Li; Zheng Dong; Mitsunori Fukuda; Mostafa Khater; Guangyu Wu
• Keywords: 0301 basic medicine; Binding Sites; QH301-705.5; Golgi Apparatus; Endoplasmic Reticulum; Article; Receptors, G-Protein-Coupled; Protein Transport; 03 medical and health sciences; HEK293 Cells; rab GTP-Binding Proteins; MCF-7 Cells; Humans; Biology (General); Protein Binding

G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER) to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.