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Agonist-induced changes in RalA activities allows the prediction of the endocytosis of G protein-coupled receptors
- Source :
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. (1):77-90
- Publisher :
- Elsevier B.V.
-
Abstract
- GTP binding proteins are classified into two families: heterotrimeric large G proteins which are composed of three subunits, and one subunit of small G proteins. Roles of small G proteins in the intracellular trafficking of G protein-coupled receptors (GPCRs) were studied. Among various small G proteins tested, GTP-bound form (G23V) of RalA inhibited the internalization of dopamine D2 receptor independently of the previously reported downstream effectors of RalA, such as Ral-binding protein 1 and PLD. With high affinity for GRK2, active RalA inhibited the GPCR endocytosis by sequestering the GRK2 from receptors. When it was tested for several GPCRs including an endogenous GPCR, lysophosphatidic acid receptor 1, agonist-induced conversion of GTP-bound to GDP-bound RalA, which presumably releases the sequestered GRK2, was observed selectively with the GPCRs which have tendency to undergo endocytosis. Conversion of RalA from active to inactive state occurred by translocation of RGL, a guanine nucleotide exchange factor, from the plasma membrane to cytosol as a complex with Gβγ. These results suggest that agonist-induced Gβγ-mediated conversion of RalA from the GTP-bound form to the GDP-bound form could be a mechanism to facilitate agonist-induced internalization of GPCRs.
- Subjects :
- 0301 basic medicine
G-Protein-Coupled Receptor Kinase 2
G protein
media_common.quotation_subject
Small G Protein
Biology
03 medical and health sciences
Angiotensin
GTP-binding protein regulators
Heterotrimeric G protein
Humans
Receptors, Lysophosphatidic Acid
Internalization
Molecular Biology
β-Adrenoceptor
media_common
G protein-coupled receptor
Receptors, Dopamine D2
β-Arrestin
Cell Biology
Epsin
Endocytosis
RALA
Cell biology
LPA
Protein Transport
HEK293 Cells
030104 developmental biology
Ral GTP-Binding Proteins
ral GTP-Binding Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 01674889
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Accession number :
- edsair.doi.dedup.....010403fb2c99ccd053af244727bd3742
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2015.10.007