Abstract
The role of Gαs in G protein-coupled receptor (GPCR) signalling at the cell surface is well established. Recent evidence has revealed the presence of Gαs on endosomes and its capacity to elicit GPCR-promoted signalling from this intracellular compartment. Here, we report an unconventional role for Gαs in the endocytic sorting of GPCRs to lysosomes. Cellular depletion of Gαs specifically delays the lysosomal degradation of GPCRs by disrupting the transfer of GPCRs into the intraluminal vesicles (ILVs) of multivesicular bodies. We show that Gαs interacts with GPCR-associated binding protein-1 (GASP1) and dysbindin, two key proteins that serve as linkers between GPCRs and the endosomal-sorting complex required for transport (ESCRT) machinery involved in receptor sorting into ILVs. Our findings reveal that Gαs plays a role in both GPCR signalling and trafficking pathways, providing another piece in the intertwining molecular network between these processes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COS Cells
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Chlorocebus aethiops
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Dysbindin
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Dystrophin-Associated Proteins / genetics
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Dystrophin-Associated Proteins / metabolism*
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Endosomes / metabolism*
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GTP-Binding Protein alpha Subunits / antagonists & inhibitors
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GTP-Binding Protein alpha Subunits / genetics
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GTP-Binding Protein alpha Subunits / metabolism*
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Gene Expression Regulation
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HEK293 Cells
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Humans
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Intercellular Signaling Peptides and Proteins
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Lysosomes / metabolism*
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Protein Transport
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Proteins / genetics
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Proteins / metabolism*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Receptors, CXCR4 / genetics
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Receptors, CXCR4 / metabolism*
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Signal Transduction
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Transport Vesicles / metabolism
Substances
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CXCR4 protein, human
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DTNBP1 protein, human
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Dysbindin
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Dystrophin-Associated Proteins
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GTP-Binding Protein alpha Subunits
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Intercellular Signaling Peptides and Proteins
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Proteins
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RNA, Small Interfering
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Receptors, CXCR4
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WFIKKN2 protein, human