Role of heterotrimeric G proteins in membrane traffic.

Bomsel, Morgane; Mostov, Keith E.

doi:10.1091/mbc.3.12.1317

Cited by 207 publications

(149 citation statements)

References 83 publications

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“…Previous studies have shown that Cav1 is able to recognize, recruit into caveolae, and regulate the activity of proteins involved in signal transduction, among which are heterotrimeric G-proteins and Src kinases (Okamoto et al, 1998). Because some of these signaling molecules regulate transcytosis of pIgR (Bomsel and Mostov, 1992;, we reasoned that m␤CD-treatment augments transcytosis by activating Cav1-associated signaling pathways. Particularly interesting in this context is the observation that phosphorylation of Cav1 on tyrosine 14 is markedly augmented in cholesterol-depleted cells (see Figure 7 and Kim et al, 2002).…”

Section: Lipid Rafts and Postendocytic Trafficmentioning

confidence: 99%

Cholesterol-sensitive Modulation of Transcytosis

Leyt

Melamed-Book

Vaerman

et al. 2007

MBoC

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Cholesterol-rich membrane domains (e.g., lipid rafts) are thought to act as molecular sorting machines, capable of coordinating the organization of signal transduction pathways within limited regions of the plasma membrane and organelles. The significance of these domains in polarized postendocytic sorting is currently not understood. We show that dimeric IgA stimulates the incorporation of its receptor into cholesterol-sensitive detergent-resistant membranes confined to the basolateral surface/basolateral endosomes. A fraction of human transferrin receptor was also found in basolateral detergent-resistant membranes. Disrupting these membrane domains by cholesterol depletion (using methyl-␤-cyclodextrin) before ligand-receptor internalization caused depolarization of traffic from endosomes, suggesting that cholesterol in basolateral lipid rafts plays a role in polarized sorting after endocytosis. In contrast, cholesterol depletion performed after ligand internalization stimulated cargo transcytosis. It also stimulated caveolin-1 phosphorylation on tyrosine 14 and the appearance of the activated protein in dimeric IgA-containing apical organelles. We propose that cholesterol depletion stimulates the coupling of transcytotic and caveolin-1 signaling pathways, consequently prompting the membranes to shuttle from endosomes to the plasma membrane. This process may represent a unique compensatory mechanism required to maintain cholesterol balance on the cell surface of polarized epithelia. INTRODUCTIONIn humans, the major antibody that mediates immunological defense against mucosal infections is dimeric IgA (dIgA). This antibody is produced by plasma cells in the lamina propria located underneath the mucosal surface (reviewed in Lamm et al., 1995;Rojas and Apodaca, 2002) and is carried from the blood to mucosal secretions by the polymeric immunoglobulin receptor (pIgR). The itinerary of pIgR and its ligand was intensively studied in the polarized MadinDarby canine kidney (MDCK) cell line that heterologously expresses rabbit pIgR (for a recent review, see Rojas and Apodaca, 2002). The receptor is initially delivered from the trans-Golgi network (TGN) to the basolateral plasma membrane, where it encounters and binds dIgA. The complex is subsequently internalized and transcytosed to the apical plasma membrane of the cell. At that surface, the ectodomain of pIgR is proteolytically cleaved off to yield the secretory component (SC), which is released together with dIgA into mucosal secretions. In the course of transcytosis, pIgRdIgA complexes traverse various endosomal compartments, among which is an endocytic compartment located immediately underneath the apical surface (Gibson et al., 1998). This apical compartment, defined as apical recycling endosomes (AREs), is enriched in dIgA and is relatively deficient in recycling transferrin (Apodaca et al., 1994;Barroso and Sztul, 1994;Brown et al., 2000). AREs are thought to play a unique role in transcytosis, possibly by exploiting apical recycling mechanisms to shuttle transcy...

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Section: Lipid Rafts and Postendocytic Trafficmentioning

confidence: 99%

Cholesterol-sensitive Modulation of Transcytosis

Leyt

Melamed-Book

Vaerman

et al. 2007

MBoC

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“…For pertussis toxin (Sigma) treatment, two conditions were used which yielded the same results, either 200 ng/ml before (16 h) and throughout the experiment (38) or 1 g/ml toxin throughout the experiment (39). For cholera toxin (Sigma) treatment, two conditions were also tested which yielded the same results, 10 g/ml toxin during the pulse (39,40) or 2 g/ml before (3 h) and throughout the experiment (41). AlF 4 Ϫ was prepared as described (42) and added during the first hour of chase.…”

Section: Verification Of the Polarized Phenotype Of Transfected Mdck mentioning

confidence: 99%

“…After extensive washing at 4°C, the filters were then transferred to a 12-well culture plate and fresh PBS, 1% BSA (200 l) was added to both the apical and the basolateral chambers (41). The apical medium was replaced after 30, 60, and 90 min, and the radioactivity present in all fractions was counted.…”

Section: Verification Of the Polarized Phenotype Of Transfected Mdck mentioning

confidence: 99%

Basolateral Localization and Transcytosis of Gonadotropin and Thyrotropin Receptors Expressed in Madin-Darby Canine Kidney Cells

Beau

Misrahi

Gross

et al. 1997

Journal of Biological Chemistry

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؊ and cholera toxin. G s activation provoked a similar effect on LH receptor distribution in MDCK cells, whereas it did not modify the compartmentalization of the TSH receptor. Hormone-specific transcytosis was observed in MDCK cells expressing the gonadotropin (FSH and LH) receptors and was increased after cholera toxin administration.The gonadotropin (LH 1 and FSH) and thyrotropin (TSH) receptors belong to the large family of G-protein-coupled receptors (1-4). They possess the distinctive seven transmembrane spanning domains. However, they form a specific subgroup characterized by the presence of a large extracellular domain constituted by the repetition of leucine-rich motif (5). This ectodomain is responsible for the high affinity hormone binding (6 -9). Gonadotropin and TSH receptors are mainly coupled to G s and thus activate adenylate cyclase. The same receptors are also able to activate phospholipase C at high hormone concentrations. Mutations of the receptors have been described leading either to their constitutive activation (10 -12) or in contrast to a loss of receptor function (13)(14)(15).Little is known about the cellular trafficking of G-proteincoupled receptors in general and of this subgroup of receptors in particular. Ultrastructural immunocytochemistry has been used to analyze the internalization mechanisms of some receptors (16 -18). LH receptor-driven hormone transcytosis was observed through endothelial cells of testicular blood vessels (19). Recently immunocytochemistry using specific monoclonal antibodies demonstrated the basolateral distribution of the TSH receptor in thyroid cells (20) and of the FSH receptor in Sertoli cells (21), whereas the LH receptor was present all over the cell surface of thecal, granulosa, and luteal cells in the ovary and Leydig cells in the testes (22,23).The question was thus raised as to whether these differences in cellular distribution were due to differences in the structure of receptors or simply secondary to the fact that thyroid follicular cells and Sertoli cells are polarized, whereas the LH receptor-expressing cells are not polarized. Another question raised was whether the mechanisms of receptor basolateral delivery were cell-specific or whether the receptors contained specific signals that could direct them to this membrane compartment in any polarized cell. To answer these questions we have established MDCK cell lines that express the FSH, LH, and TSH receptors. Using these models we have analyzed the distribution of the receptors in polarized monolayers. MATERIALS AND METHODSCell Culture-MDCK cells (type II) were seeded and grown on coverslips (Nunc) or filters (0.4-m polycarbonate, tissue culture-treated, Transwell costar) as described previously (24,25).Antireceptor Antibodies-Mouse monoclonal antibodies FSHR323 (21), LHR38 (26),27) recognize an epitope in the extracellular domain of the FSH, LH, and TSH receptors, respectively. Antibody T3-365 has been raised against the intracellular domain of the TSH receptor (20). The rabbit polyclonal TSHR...

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“…2 Transcytosis of pIgR and other molecules is stimulated either by activation of protein kinase C (10) or by increase in intracellular free Ca 2ϩ , 3 so both arms of the phospholipase C signaling pathway may redundantly stimulate transcytosis. Delivery to the apical surface, either by transcytosis or directly from the TGN, is also stimulated by the heterotrimeric G protein, G s (11,12), as well as cAMP and protein kinase A (13,14). Both the G s ␣ and G␤␥ subunits are stimulatory, at least for transcytotic apical delivery (11).…”

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confidence: 99%

“…Delivery to the apical surface, either by transcytosis or directly from the TGN, is also stimulated by the heterotrimeric G protein, G s (11,12), as well as cAMP and protein kinase A (13,14). Both the G s ␣ and G␤␥ subunits are stimulatory, at least for transcytotic apical delivery (11). Transcytosis in MDCK cells is stimulated by bradykinin, 3 while in animals transcytosis is stimulated by several hormones and neurotransmitters (15)(16)(17)(18).…”

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confidence: 99%

Calmodulin Binds to the Basolateral Targeting Signal of the Polymeric Immunoglobulin Receptor

Chapin

Enrich

Aroeti

et al. 1996

Journal of Biological Chemistry

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We have identified a major calmodulin (CaM)-binding protein in rat liver endosomes using 125 I-CaM overlays from two-dimensional protein blots. Immunostaining of blots demonstrates that this protein is the polymeric immunoglobulin receptor (pIgR). We further investigated the interaction between pIgR and CaM using Madin-Darby canine kidney cells stably expressing cloned wild-type and mutant pIgR. We found that detergent-solubilized pIgR binds to CaM-agarose in a Ca 2؉ -dependent fashion, and binding is inhibited by the addition of excess free CaM or the CaM antagonist W-13 (N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide), suggesting that pIgR binding to CaM is specific. The plasma membrane of polarized epithelial cells is divided into apical and basolateral surfaces, each having a distinct protein and lipid composition. Cells use two pathways to deliver proteins to the correct surface. First, newly made proteins are packaged in the trans-Golgi network (TGN) 1 into vesicles that deliver them directly to either the apical or basolateral surface. Second, proteins can be delivered first to one surface and then endocytosed and transcytosed to the opposite surface. At least in the well polarized Madin-Darby canine kidney (MDCK) cell line, targeting to the basolateral surface generally requires a sorting signal located in the cytoplasmic domain of the protein. For a number of basolateral proteins it has been found that mutations in the cytoplasmic domain prevent TGN to basolateral targeting (1). The first basolateral signal to be identified is the 17-amino acid membrane proximal segment (residues 653-670) of the cytoplasmic domain of the polymeric immunoglobulin receptor (pIgR) (2). This protein is normally delivered from the TGN to the basolateral surface, and then endocytosed and transcytosed to the apical surface. Deletion of most of this 17-residue segment prevents TGN to basolateral delivery. Moreover, this segment can be transplanted to a heterologous reporter molecule, which is then retargeted from the apical to the basolateral surface (2). In at least one other case, the low density lipoprotein receptor, autonomous basolateral sorting signals have been identified (3).The pIgR basolateral targeting signal has been systematically analyzed by alanine scanning mutagenesis (4). Mutation of His-656, Arg-657, or Val-660 to Ala substantially diminishes, but does not eliminate, TGN to basolateral targeting. Mutation of other residues had little or no effect. The structure of a synthetic 17-residue peptide corresponding to this signal has been determined by two-dimensional nuclear magnetic resonance spectroscopy (4). This peptide tends to adopt a putative type 1 ␤-turn, encompassing residues 658 -661, followed by a nascent helical structure. In MDCK cells polarized sorting takes place in both the TGN and after endocytosis. Mutations that diminish TGN to basolateral sorting and increase TGN to apical sorting have a similar effect on sorting in the endocytotic pathway, decreasing recycling to the basolateral surface and...

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Role of heterotrimeric G proteins in membrane traffic.

Cited by 207 publications

References 83 publications

Cholesterol-sensitive Modulation of Transcytosis

Cholesterol-sensitive Modulation of Transcytosis

Basolateral Localization and Transcytosis of Gonadotropin and Thyrotropin Receptors Expressed in Madin-Darby Canine Kidney Cells

Calmodulin Binds to the Basolateral Targeting Signal of the Polymeric Immunoglobulin Receptor

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