Rab8 interacts with distinct motifs in α2B- and β2-adrenergic receptors and differentially modulates their transport

Chunmin Dong, Lingling Yang, Xiaoping Zhang, Hua Gu, May L. Lam, William C. Claycomb, Houhui Xia, Guangyu Wu

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The molecular mechanism underlying the post-Golgi transport of G protein-coupled receptors (GPCRs) remains poorly understood. Here we determine the role of Rab8 GTPase, which modulates vesicular protein transport between the trans-Golgi network (TGN) and the plasma membrane, in the cell surface targeting of α2B- and β2-adrenergic receptors (AR). Transient expression of GDP- and GTP-bound Rab8 mutants and short hairpin RNA-mediated knockdown of Rab8 more potently inhibited the cell surface expression of α2B-AR than β2-AR. The GDP-bound Rab8(T22N) mutant attenuated ERK1/2 activation by α2B-AR, but not β2-AR, and arrested α2B-AR in the TGN compartment. Co-immunoprecipitation revealed that both α2B-AR and β2-AR physically interacted with Rab8 and glutathione S-transferase fusion protein pulldown assays demonstrated that Rab8 interacted with the C termini of both receptors. Interestingly, mutation of the highly conserved membrane-proximal C terminus dileucine motif selectively blocked β2-AR interaction with Rab8, whereas mutation of residues Val431-Phe432-Asn433-Gln434, Pro447-Trp448, Gln450-Thr451, and Trp453 in the C terminus impaired α2B-AR interaction with Rab8. Furthermore, transport inhibition by Rab8(T22N) of a chimeric β2-AR carrying the α2B-AR C terminus was similar to α2B-AR. These data provide strong evidence indicating that Rab8 GTPase interacts with distinct motifs in the C termini of α2B-AR and β2-AR and differentially modulates their traffic from the TGN to the cell surface.

Original languageEnglish (US)
Pages (from-to)20369-20380
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number26
DOIs
StatePublished - Jun 25 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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