Specific TBC Domain-Containing Proteins Control the ER-Golgi-Plasma Membrane Trafficking of GPCRs

Zhe Wei, Maoxiang Zhang, Chunman Li, Wei Huang, Yi Fan, Jianhui Guo, Mostafa Khater, Mitsunori Fukuda, Zheng Dong, Gang Hu, Guangyu Wu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell surface signaling proteins. However, the molecular mechanisms underlying their cell surface delivery after synthesis remain poorly understood. Here, we screen the TBC domain-containing proteins, putative Rab GTPase-activating proteins (GAPs), in the intracellular trafficking of GPCRs and identify several TBC proteins that activity-dependently regulate the anterograde transport, en route from the endoplasmic reticulum to the Golgi or from the Golgi to the cell surface, of several prototypic GPCR members without affecting other plasma membrane proteins. We also show that TBC1D6 functions as a GAP for Rab26, physically associates with Rab26, and attenuates Rab26 interaction with GPCRs. Furthermore, both overexpression and depletion of TBC1D6 inhibit the post-Golgi traffic of GPCRs. These data demonstrate important roles of the TBC proteins in forward trafficking of nascent GPCRs and reveal regulatory mechanisms of GPCR targeting to the functional destination. Wei et al. report that several TBC proteins specifically and activity-dependently regulate ER-Golgi-plasma membrane transport of nascent GPCRs. They also show that TBC1D6 is a GAP for Rab26 and controls GPCR post-Golgi traffic. Their results reveal crucial roles of TBC proteins in and provide regulatory mechanisms of GPCR trafficking.

Original languageEnglish (US)
Pages (from-to)554-566.e4
JournalCell Reports
Volume28
Issue number2
DOIs
StatePublished - Jul 9 2019

Keywords

  • ER
  • G-protein-coupled receptor
  • Golgi
  • Rab GTPase
  • RabGAP
  • TBC protein
  • TBC1D6
  • anterograde export
  • plasma membrane
  • trafficking

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wei, Z., Zhang, M., Li, C., Huang, W., Fan, Y., Guo, J., Khater, M., Fukuda, M., Dong, Z., Hu, G., & Wu, G. (2019). Specific TBC Domain-Containing Proteins Control the ER-Golgi-Plasma Membrane Trafficking of GPCRs. Cell Reports, 28(2), 554-566.e4. https://doi.org/10.1016/j.celrep.2019.05.033