Ligand-induced caveolae-mediated internalization of A1 adenosine receptors: morphological evidence of endosomal sorting and receptor recycling

Escriche, Marisol; Burgueño, Javier; Ciruela, Francisco; Canela, Enric I.; Mallol, Josefa; Enrich, Carlos; Lluı́s, Carmen

doi:10.1016/s0014-4827(02)00090-3

Cited by 67 publications

(56 citation statements)

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“…When the role of Cav-1 in knockout mice was investigated, the calcium-dependent contractile response of arteries ANOVA test were employed for statistical difference among groups. P P to angotensin II, endothelin-1 and phorbol ester was attenuated (Escriche et al, 2003). This result suggests Cav-1 may be concerned with physiological phenomena that are related to calcium homeostasis in the body.…”

Section: Discussionmentioning

confidence: 81%

“…In speculation, another possible regulatory mechanism of caveolin for the function of receptor related with caveolin was the internalization of the caveolinanchored receptor proteins (Okamoto et al, 2000;Escriche et al, 2003). There are many reports on receptor internalization by the activation of protein kinase C (PKC) (Mundell et al, 2003;Montiel et al, 2004;Saito et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Vol. 37(2), 91-100, 2005 to angotensin II, endothelin-1 and phorbol ester was attenuated (Escriche et al, 2003). This result suggests Cav-1 may be concerned with physiological phenomena that are related to calcium homeostasis in the body.…”

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confidence: 85%

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Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Jung

Kwak²,

Kim³

et al. 2005

Exp Mol Med

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A bstractThe calcium sensing receptor (C aSR ) plays an im portant role for sensing local changes in the extracellular calcium concentration ([C a 2+ ] o ) in bone rem odeling. A lthough the function of C aSR is know n, the regulatory m echanism of C aSR rem ains controversial. W e report here the regulatory effect of caveolin on C aSR function as a process of C aSR regulation by using the hum an osteosarcom a cell line (Saos-2). The intracellular calcium concentration ([C Keyw ords: antisense oligodeoxynucleotides; calcium sensing receptor; caveolae; caveolin-1; confocal microscopy; osteosarcoma cell linea IntroductionExtracellular calcium is essential for a number of vital processes, including bone mineralization, blood coagulation, regulation of enzymatic activity, and the modulation of permeability and excitability of the plasma membranes. For these reasons, the calcium concentration in extracellular fluids is under strict control by a complex homeostatic system that includes the bones, kidney, intestines, parathyroid and thyroid glands (Brown, 1991). The extracellular calcium sensing receptor (CaSR) is an essential component of this system for regulating parathyroid hormone secretion, Ca 2+ excretion by the kidney and bone remodeling. The CaSR belongs to the type III family of G-proteincoupled receptors, which comprises the metabotropic glutamate receptor and putative vomeronasal organ receptors (Brown et al., 1993). Several lines of evidence have suggested that an increase in local Calcium sensing receptor form s com plex with and is up-regulated by caveolin-1 in cultured hum an osteosarcom a (Saos-2) cells 92 Exp. Mol. Med. Vol. 37(2), [91][92][93][94][95][96][97][98][99][100] 2005 calcium concentration in the resorption lacunae suppresses osteoclastic bone-resorbing activity through an increase in intracellular calcium; this is mediated through a ryanodine-like receptor (Zaidi et al., 1989;1991;1993;Adebanjo et al., 1994;Shin et al., 2003) and the CaSR regulates osteoclastic bone resorption (Kameda et al., 1998).Caveolae are plasma membrane organelles that are characterized by a low solubility in Triton X-100 and these are the organelles where specific lipid and protein components are subcompartmentalized (Kurzchalia and Parton, 1999). Caveolin (Cav), a 21-to 24-kDa integral membrane protein, is a principal component of the caveolae membrane and it exists as several isoforms (Cav-1, -2, and -3) (Okamoto et al., 1998;Kurzchalia and Parton, 1999). Recent studies have shown that functional proteins including receptors are localized in the caveolae by being anchored through the caveolins (Li et al., 1995; GarciaCardena et al., 1996;Couet et al., 1997;Lee et al., 2001;Cha et al., 2004). In bone, there is no evidence of the interaction between caveolin and CaSR, and for the regulatory effect of caveolin on CaSR function.The purpose of present study, therefore, is to demonstrate the relationship between CaSR and caveolins in the osteosarcoma cell line (Saos-2). Our results show that CaSR protein is co-locali...

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Jung

Kwak²,

Kim³

et al. 2005

Exp Mol Med

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“…Lipid raft endocytosis, initially characterized as an entry route for pathogens (Pelkmans et al, 2001), toxins (Montesano et al, 1982), extracellular ligands (Benlimame et al, 1998), and molecules such as glycosyl phosphatidylinositolanchored proteins (Nichols et al, 2001) and sphingolipids (Puri et al, 2001), has recently been implicated as a potential pathway for GPCR endocytosis (Escriche et al, 2003;OlliLahdesmaki et al, 2003;Pawson et al, 2003;Venkatesan et al, 2003). Nevertheless, little is known about how GPCRs are trafficked and recycled via this mechanism or how this alternative internalization pathway influences GPCR desensitization.…”

Section: Introductionmentioning

confidence: 99%

“…These actions in turn promote uncoupling of the GPCR from G proteins and effectors (desensitization) and subsequent internalization via clathrincoated pits, where trafficking to acidic early endosomes leads to recycling of the resensitized GPCR back to the cell surface, or targets the receptor for degradation (for review, see Ferguson, 2001). However, recent studies suggest that GPCR trafficking and signaling may, in some instances, be regulated by clathrin-independent pathways (Malecz et al, 1998;Walker et al, 1999;Pao and Benovic, 2002).Lipid raft endocytosis, initially characterized as an entry route for pathogens (Pelkmans et al, 2001), toxins (Montesano et al, 1982), extracellular ligands (Benlimame et al, 1998), and molecules such as glycosyl phosphatidylinositolanchored proteins (Nichols et al, 2001) and sphingolipids (Puri et al, 2001), has recently been implicated as a potential pathway for GPCR endocytosis (Escriche et al, 2003; OlliLahdesmaki et al, 2003;Pawson et al, 2003;Venkatesan et al, 2003). Nevertheless, little is known about how GPCRs are trafficked and recycled via this mechanism or how this alternative internalization pathway influences GPCR desensitization.…”

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confidence: 99%

Lipid Raft-dependent Glucagon-like Peptide-2 Receptor Trafficking Occurs Independently of Agonist-induced Desensitization

Estall

Yusta

Drucker

2004

MBoC

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The intestinotrophic and cytoprotective actions of glucagon-like peptide-2 (GLP-2) are mediated by the GLP-2 receptor (GLP-2R), a member of the class II glucagon-secretin G protein-coupled receptor superfamily. Although native GLP-2 exhibits a short circulating half-life, long-acting degradation-resistant GLP-2 analogues are being evaluated for therapeutic use in human subjects. Accordingly, we examined the mechanisms regulating signaling, internalization, and trafficking of the GLP-2R to identify determinants of receptor activation and desensitization. Heterologous cells expressing the transfected rat or human GLP-2R exhibited a rapid, dose-dependent, and prolonged desensitization of the GLP-2-stimulated cAMP response and a sustained GLP-2-induced decrease in levels of cell surface receptor. Surprisingly, inhibitors of clathrin-dependent endocytosis failed to significantly decrease GLP-2R internalization, whereas cholesterol sequestration inhibited ligand-induced receptor internalization and potentiated homologous desensitization. The hGLP-2R localized to both Triton X-100 -soluble and -insoluble (lipid raft) cellular fractions and colocalized transiently with the lipid raft marker caveolin-1. Although GLP-2R endocytosis was dependent on lipid raft integrity, the receptor transiently associated with green fluorescent protein tagged-early endosome antigen 1-positive vesicles and inhibitors of endosomal acidification attenuated the reappearance of the GLP-2R on the cell surface. Our data demonstrate that GLP-2R desensitization and raft-dependent trafficking represent distinct and independent cellular mechanisms and provide new evidence implicating the importance of a clathrin-and dynamin-independent, lipid raft-dependent pathway for homologous G protein-coupled receptor internalization. INTRODUCTIONGlucagon-like peptide-2 (GLP-2) is a peptide hormone produced via posttranslational processing of proglucagon and is secreted from intestinal L-cells after nutrient intake (Drucker, 2001). GLP-2 stimulates crypt cell proliferation and inhibits apoptosis in the gut mucosal epithelium (Drucker et al., 1996;Tsai et al., 1997). The biological actions of GLP-2 are transduced by a single GLP-2 receptor (GLP-2R), a member of the class II glucagon-secretin G proteincoupled receptor (GPCR) superfamily , which includes structurally related hormone receptors for peptides such as glucagon, GLP-1, and secretin (Mayo et al., 2003). The GLP-2R is expressed in human enteroendocrine cells (Yusta et al., 2000b), murine enteric neurons (Bjerknes and Cheng, 2001), and in specific regions of the central nervous system (Tang-Christensen et al., 2000;Lovshin et al., 2001). Agonist-induced activation of the GLP-2R is coupled to generation of cAMP (Yusta et al., 1999) and leads to enhanced cell survival via inhibition of the proapoptotic molecules GSK3 and Bad (Yusta et al., 2002).GPCRs share a common regulatory pathway that governs agonist-induced desensitization and endocytosis. This pathway, originally described for many of the class I GPCR...

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Light resonance energy transfer‐based methods in the study of G protein‐coupled receptor oligomerization

et al. 2007

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Since most of the functions in cells are mediated by multimeric protein complexes, the determination of protein-protein interactions is an important step in the study of cellular mechanisms. Traditionally, after screening for possible target interactors by means of a yeast two-hybrid screen, several methods are used to validate the initial result before carrying out functional experiments. Nowadays, non-invasive fluorescence-based methods like Bioluminescence Resonance Energy Transfer (BRET) and Fluorescence Resonance Energy Transfer (FRET) are widely used in the study of protein-protein interactions in living cells. In the present review, we address the individual strengths and weaknesses of both RET approaches, providing information on their possible future use in the study of G protein-coupled receptor oligomerization.

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Ligand-induced caveolae-mediated internalization of A1 adenosine receptors: morphological evidence of endosomal sorting and receptor recycling

Cited by 67 publications

References 57 publications

Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Lipid Raft-dependent Glucagon-like Peptide-2 Receptor Trafficking Occurs Independently of Agonist-induced Desensitization

Light resonance energy transfer‐based methods in the study of G protein‐coupled receptor oligomerization

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