α2B-Adrenergic receptor interaction with tubulin controls its transport from the endoplasmic reticulum to the cell surface

Matthew T. Duvernay, Hong Wang, Chunmin Dong, Jesse J. Guidry, Dan L. Sackett, Guangyu Wu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

It is well recognized that the C terminus (CT) plays a crucial role in modulating G protein-coupled receptor (GPCR) transport from the endoplasmic reticulum (ER) to the cell surface. However the molecular mechanisms that govern CT-dependent ER export remain elusive. To address this issue, we used α2Badrenergic receptor (α2B-AR) as a model GPCR to search for proteins interacting with the CT. By using peptide-conjugated affinity matrix combined with proteomics and glutathione S-transferase fusion protein pull-down assays, we identified tubulin directly interacting with the α2B-AR CT. The interaction domains were mapped to the acidic CT of tubulin and the basic Arg residues in the α2B-AR CT, particularly Arg-437, Arg-441, and Arg-446. More importantly, mutation of these Arg residues to disrupt tubulin interaction markedly inhibited α2B-AR transport to the cell surface and strongly arrested the receptor in the ER. These data provide the first evidence indicating that the α2B-AR C-terminal Arg cluster mediates its association with tubulin to coordinate its ER-to-cell surface traffic and suggest a novel mechanism of GPCR export through physical contact with microtubules.

Original languageEnglish (US)
Pages (from-to)14080-14089
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number16
DOIs
StatePublished - Apr 22 2011

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Tubulin
Endoplasmic Reticulum
Adrenergic Receptors
G-Protein-Coupled Receptors
Glutathione Transferase
Microtubules
Proteomics
Assays
Proteins
Fusion reactions
Association reactions
Peptides
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

α2B-Adrenergic receptor interaction with tubulin controls its transport from the endoplasmic reticulum to the cell surface. / Duvernay, Matthew T.; Wang, Hong; Dong, Chunmin; Guidry, Jesse J.; Sackett, Dan L.; Wu, Guangyu.

In: Journal of Biological Chemistry, Vol. 286, No. 16, 22.04.2011, p. 14080-14089.

Research output: Contribution to journalArticle

Duvernay, Matthew T. ; Wang, Hong ; Dong, Chunmin ; Guidry, Jesse J. ; Sackett, Dan L. ; Wu, Guangyu. / α2B-Adrenergic receptor interaction with tubulin controls its transport from the endoplasmic reticulum to the cell surface. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 16. pp. 14080-14089.
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