An escort for GPCRs: implications for regulation of receptor density at the cell surface

Achour, Lamia; Labbé-Jullié, Catherine; Scott, Mark G. H.; Marullo, Stéfano

doi:10.1016/j.tips.2008.07.009

Cited by 98 publications

(88 citation statements)

References 82 publications

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“…2D), which also indicated the D1R-YFP internalization caused by drug treatments. 3.3 D5R did not translocate to cell surface from intracellular compartments after the treatment It has been reported that the GPCRs can not only be internalized from the cell surface but also display the regulated translocation to the cell surface from intracellular compartments [11] . As D5R locates both in the plasma membrane and in the intracellular compartments in resting conditions, there raises the question: whether D5R would be translocated by the drug treatment?…”

mentioning

confidence: 91%

“…The trafficking of GPCRs between cell surface and intracellular compartment indicates an important functional regulation [11] . Two situations are included in the trafficking process: one is the internalization of the receptor from the cell surface to the intracellular compartment; the other is the translocation to cell surface from the intracellular compartment.…”

Section: Introductionmentioning

confidence: 99%

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神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

Jin

2009

Neurosci. Bull.

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Objective To explore the possible differential trafficking properties of the dopamine D1-like receptor subtypes, D1 receptor and D5 receptor. Methods To visualize distributions of dopamine D1-like receptor subtypes at subcellular level, the yellow and cyan variants of green fluorescent protein (GFP) were used to tag D1 and D5 receptors. After transfection with the tagged dopamine receptors, the neuroblastoma cells NG108-15 were treated with D1 agonist SKF38393 or acetylcholine (ACh). Then we observed the subcellular distributions of the tagged receptors under the confocal microscopy and tried to determine trafficking properties by comparing their distribution patterns before and after the drug treatment. Results In resting conditions, D1 receptors located in the plasma membrane of NG108-15 cells, while D5 receptors located in both plasma membrane and cytosol. With the pre-treatment of SKF38393, the subcellular distribution of D1 receptors was changed. The yellow particle-like fluorescence of tagged D1 receptors appeared in the cytosol, indicating that D1 receptors were internalized into cytosol from the cell surface. Same situation also occurred in ACh pre-treatment. In contrast, the subcellular distribution of D5 receptors was not changed after SKF38393 or ACh treatment, indicating that D5R was not translocated to cell surface. Interestingly, when D1 and D5 receptors were co-expressed in the same cell, both kept their distinct subcellular distribution patterns and the trafficking properties. Conclusion Our present study reveals that in NG108-15 nerve cells, dopamine D1 and D5 receptors exhibit differential subcellular distribution patterns, and only D1 receptor has a marked trafficking response to the drug stimulation. We further discuss the potential role of the differential trafficking properties of D1-like receptors in complex modulation of DA signaling.

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confidence: 91%

Section: Introductionmentioning

confidence: 99%

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

Jin

2009

Neurosci. Bull.

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“…Most GPCRs are found as stocks of functional receptors retained mainly in the ER or Golgi apparatus. These GPCRs are mobilized to the cell surface by their interactions with escort proteins (26,27). For instance, the receptor activity-modifying protein 2 (RAMP2) increases CRF 1 R (28) and RAMP1 increases calcitonin-receptor-like receptor (CRLR) (29) in the plasma membrane.…”

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confidence: 99%

CRF binding protein facilitates the presence of CRF type 2α receptor on the cell surface

Slater

Cerda

Pereira

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Corticotropin releasing factor binding protein (CRF-BP) was originally recognized as CRF sequestering protein. However, its differential subcellular localization in different brain nuclei suggests that CRF-BP may have additional functions. There is evidence that CRF-BP potentiates CRF and urocortin 1 actions through CRF type 2 receptors (CRF 2 R). CRF 2 R is a G protein-coupled receptor (GPCR) that is found mainly intracellularly as most GPCRs. The access of GPCRs to the cell surface is tightly regulated by escort proteins. We hypothesized that CRF-BP binds to CRF 2 R, exerting an escort protein role. We analyzed the colocalization of CRF-BP and CRF 2 R in cultured rat mesencephalic neurons, and the localization and interaction of heterologous expressed CRF-BP and CRF 2α R in yeast, human embryonic kidney 293, and rat pheochromocytoma 12 cells. Our results showed that CRF-BP and CRF 2 R naturally colocalize in the neurites of cultured mesencephalic neurons. Heterologous expression of each protein showed that CRF-BP was localized mainly in secretory granules and CRF 2α R in the endoplasmic reticulum. In contrast, CRF-BP and CRF 2α R colocalized when both proteins are coexpressed. Here we show that CRF-BP physically interacts with the CRF 2α R but not the CRF 2β R isoform, increasing CRF 2α R on the cell surface. Thus, CRF-BP emerges as a GPCR escort protein increasing the understanding of GPCR trafficking.T he corticotropin releasing factor (CRF) system plays a key role in the response and adaptation to stressful stimuli (1, 2) and in the interaction between stress and addiction (3). The CRF system acts on the hypothalamic-pituitary-adrenal axis (4, 5) and in different brain regions (1, 6). The CRF system includes four peptides, CRF type 1 (CRF 1 R) and type 2 (CRF 2 R), G protein-coupled receptors (GPCRs) (6-8), and CRF binding protein (CRF-BP) (9). CRF-BP was described as a circulating polypeptide in pregnant women (10, 11). CRF-BP binds CRF and urocortin with high affinity (12). Different functions have been proposed for CRF-BP (13). On one hand, CRF-BP exerts an inhibitory role by sequestering CRF peptide (9, 14-16). On other hand, a facilitatory role of CRF-BP on CRF-dependent neuronal plasticity depending on CRF 2 R in the rat ventral tegmental area (VTA) has been described (17, 18). Recently, it has been shown that CRF-BP and CRF 2 R are important for ethanol binge drinking behavior (19). The anatomical evidence showing that CRF-BP has different subcellular distribution depending on the neuronal context (20) further supports several roles for CRF-BP.Three isoforms of CRF 2 R have been reported, the α isoform being the most expressed in the brain (21). CRF 2α R is localized intracellularly in neurons of the rat dorsal raphe nucleus and that exposure to acute (22) and repeated stress (23) increases its presence in the plasma membrane. CRF 2α R overexpressed in human embryonic kidney (HEK293T) cells is associated with the endoplasmic reticulum (ER) (24). Schulz et al. (25) showed that CRF 2α R is retained in...

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“…Cependant, de nombreuses observations indiquent que le trafic de ces récepteurs vers la surface cellulaire pourrait être régulé par des interactions avec certaines protéines et par des signaux extra-cellulaires. Des études récentes démontrent que pour de nombreux RCPG, une proportion importante des récepteurs est retenue dans des compartiments intracellulaires comme le réticulum endoplasmique (RE) ou l'appareil de Golgi [1]. Ces « réserves » peuvent être mobilisables vers la membrane plasmique en réponse à une stimulation physiologique qui nécessite une augmentation rapide de la réceptivité cellulaire [2,3].…”

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“…De plus, dans des expériences d'expression des RCPG dans des cellules modèles ne les exprimant pas naturellement (expression hétérologue), il a été montré que beaucoup d'entre eux nécessitent une association à des protéines d'escorte ou à des chaperons moléculaires pour être correctement exprimés à la surface. Les récepteurs olfactifs en sont un des exemples les plus connus et cette caractéristique a pendant longtemps empêché leur étude fonctionnelle in vitro [1]. Dans plusieurs pathologies humaines, comme le diabète insipide néphrogénique, la rétinite pigmentaire, l'obésité ou l'hypogonadisme, des mutations somatiques des RCPG [4] ou de protéines nécessaires à leur maturation [5], sont à l'origine d'un excès de rétention dans les compartiments intracellulaires.…”

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Trafic cellulaire des récepteurs GABA_Bvers la membrane : PRAF2, un nouveau point de contrôle

Doly

Marullo

2015

Med Sci (Paris)

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An escort for GPCRs: implications for regulation of receptor density at the cell surface

Abstract: G-protein-coupled receptors (GPCRs

Cited by 98 publications

References 82 publications

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

CRF binding protein facilitates the presence of CRF type 2α receptor on the cell surface

Trafic cellulaire des récepteurs GABA_Bvers la membrane : PRAF2, un nouveau point de contrôle

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An escort for GPCRs: implications for regulation of receptor density at the cell surface

Abstract: G-protein-coupled receptors (GPCRs

Cited by 98 publications

References 82 publications

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

CRF binding protein facilitates the presence of CRF type 2α receptor on the cell surface

Trafic cellulaire des récepteurs GABABvers la membrane : PRAF2, un nouveau point de contrôle

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Trafic cellulaire des récepteurs GABA_Bvers la membrane : PRAF2, un nouveau point de contrôle