GGA3 interacts with a G protein-coupled receptor and modulates its cell surface export

Maoxiang Zhang, Jason E. Davis, Chunman Li, Jie Gao, Wei Huang, Nevin A Lambert, Alvin V Terry, Guangyu Wu

Research output: Contribution to journalArticle

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Abstract

Molecular mechanisms governing the anterograde trafficking of nascent G protein-coupled receptors (GPCRs) are poorly understood. Here, we have studied the regulation of cell surface transport of α2-adrenergic receptors (α2-ARs) by GGA3 (Golgi-localized, γ-adaptin ear domain homology, ADP ribosylation factor-binding protein 3), a multidomain clathrin adaptor protein that sorts cargo proteins at the trans-Golgi network (TGN) to the endosome/lysosome pathway. By using an inducible system, we demonstrated that GGA3 knockdown significantly inhibited the cell surface expression of newly synthesized α2B-AR without altering overall receptor synthesis and internalization. The receptors were arrested in the TGN. Furthermore, GGA3 knockdown attenuated α2B-AR-mediated signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) activation and cyclic AMP (cAMP) inhibition. More interestingly, GGA3 physically interacted with α2B-AR, and the interaction sites were identified as the triple Arg motif in the third intracellular loop of the receptor and the acidic motif EDWE in the VHS domain of GGA3. In contrast, α2A-AR did not interact with GGA3 and its cell surface export and signaling were not affected by GGA3 knockdown. These data reveal a novel function of GGA3 in export trafficking of a GPCR that is mediated via a specific interaction with the receptor.

Original languageEnglish (US)
Pages (from-to)1152-1163
Number of pages12
JournalMolecular and Cellular Biology
Volume36
Issue number7
DOIs
StatePublished - Apr 1 2016

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G-Protein-Coupled Receptors
trans-Golgi Network
Vesicular Transport Adaptor Proteins
ADP-Ribosylation Factors
Mitogen-Activated Protein Kinase 3
Endosomes
Mitogen-Activated Protein Kinase 1
Lysosomes
Cyclic AMP
Adrenergic Receptors
Ear
Carrier Proteins
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

GGA3 interacts with a G protein-coupled receptor and modulates its cell surface export. / Zhang, Maoxiang; Davis, Jason E.; Li, Chunman; Gao, Jie; Huang, Wei; Lambert, Nevin A; Terry, Alvin V; Wu, Guangyu.

In: Molecular and Cellular Biology, Vol. 36, No. 7, 01.04.2016, p. 1152-1163.

Research output: Contribution to journalArticle

Zhang, Maoxiang ; Davis, Jason E. ; Li, Chunman ; Gao, Jie ; Huang, Wei ; Lambert, Nevin A ; Terry, Alvin V ; Wu, Guangyu. / GGA3 interacts with a G protein-coupled receptor and modulates its cell surface export. In: Molecular and Cellular Biology. 2016 ; Vol. 36, No. 7. pp. 1152-1163.
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