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

Chunman Li, Zhe Wei, Yi Fan, Wei Huang, Yunchao Su, Honglin Li, Zheng Dong, Mitsunori Fukuda, Mostafa Khater, Guangyu Wu

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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. Li et al. report that Rab43 GTPase controls anterograde ER-Golgi transport of nascent GPCRs, as well as their sorting from other membrane proteins, which is mediated via direct interaction with the receptors. Their results suggest a mechanism of targeting and sorting of the members of the GPCR superfamily.

Original languageEnglish (US)
Pages (from-to)1089-1101
Number of pages13
JournalCell Reports
Volume21
Issue number4
DOIs
StatePublished - Oct 24 2017

Keywords

  • ER
  • G-protein-coupled receptor
  • Golgi
  • Rab GTPase
  • Rab43
  • adrenergic receptor
  • angiotensin receptor
  • anterograde export
  • sorting
  • trafficking

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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